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Pediatr Infect Dis J 2002 Nov;21(11):1008-16
 

Multinational study of pneumococcal serotypes causing acute otitis media in children.

Hausdorff WP, Yothers G, Dagan R, Kilpi T, Pelton SI, Cohen R, Jacobs MR, Kaplan SL, Levy C, Lopez EL, Mason EO Jr, Syriopoulou V, Wynne B, Bryant J

Wyeth Vaccines, West Henrietta, NY 14586, USA. Hausdowp@wyeth.com

BACKGROUND: Streptococcus pneumoniae is a major cause of acute otitis media (AOM) in young children. More than 90 immunologically distinct pneumococcal serotypes have been identified, but limited information is available regarding their relative importance in AOM. METHODS: We analyzed nine existing datasets comprising pneumococcal isolates from middle ear fluid samples collected from 1994 through 2000 from 3,232 children with AOM from Finland, France, Greece, Israel, several East European countries, the US and Argentina. We examined the distribution of pneumococcal serotypes in relation to several demographic and epidemiologic variables, including gender, age, antibiotic resistance and source of culture material. RESULTS: The major serotypes identified included 19F and 23F, each comprising 13 to 25% of pneumococcal middle ear fluid isolates in most datasets; 14 and 6B, comprising 6 to 18%; whereas 6A, 19A and 9V each comprised 5 to 10%. Despite differences in location, study design and antibiotic susceptibility, each major serotype was prominent in most age groups of each dataset. Serotypes represented in the 7-valent pneumococcal conjugate vaccine (PCV-7, 4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 60 to 70% of all pneumococcal isolates in the 6- to 59-month age range, but only 40 to 50% of isolates in children <6 or >/=60 months old. Serotype 3 and, in certain datasets, serotypes 1 and 5, were more important in the <6- and >/=60-month age groups. In each age group vaccine-related serotypes (mainly 6A and 19A) comprised an additional 10 to 15% of all pneumococcal isolates. Four serotypes (23F, 19F, 14 and 6B) accounted for 83% of all penicillin-resistant observations. CONCLUSIONS: This analysis of several geographically diverse datasets indicates that a limited number of serotypes, largely represented in PCV-7, accounted for the majority of episodes of pneumococcal AOM in children between 6 and 59 months of age. Certain serotypes appeared to be relatively more significant in children <6 months or >59 months of age.

Publication Types:
 

• Multicenter study

PMID: 12442021, UI: 22329479

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Science 2002 Dec 20;298(5602):2312-6
 

Public health. Rough-and-tumble behind Bush's smallpox policy.

Cohen J, Enserink M

Publication Types:
 

• News

PMID: 12493889, UI: 22382070

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Science 2002 Dec 20;298(5602):2300
 

Breakthrough of the year. Bioterrorism: the calm after the storm.

Enserink M

Publication Types:
 

• News

PMID: 12493879, UI: 22382060

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Vaccine 2003 Jan 17;21(5-6):562-565
 

B cell responses in gastric antrum and duodenum following oral inactivated Helicobacter pylori whole cell (HWC) vaccine and LT(R192G) in H. pylori seronegative individuals.

Losonsky GA, Kotloff KL, Walker RI

Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, 21201, Baltimore, MD, USA

[Record supplied by publisher]
 

To investigate whether B cell-specific responses could be elicited in the gastric mucosa of Helicobacter pylori (HP) naive subjects, five volunteers ingested three doses of a HP killed whole cell (HWC) vaccine with 25&mgr;g of recombinant heat-labile toxin (LT(R192G)). Two of three subjects had detectable LT(R192G) and HWC IgA antibody secreting cell (ASC) gastric responses. LT(R192G) and HWC responses in duodenal were 5-14-fold higher than those detected in antral biopsies (P<0.01 and P=0.05, respectively). These results provide the first evidence that specific gastric B cell responses can be induced in HP-non-infected individuals following oral immunization.

PMID: 12531656

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Vaccine 2003 Jan 17;21(5-6):538-48
 

Salmonella typhi and S. typhimurium derivatives harbouring deletions in aromatic biosynthesis and Salmonella Pathogenicity Island-2 (SPI-2) genes as vaccines and vectors.

Khan SA, Stratford R, Wu T, Mckelvie N, Bellaby T, Hindle Z, Sinha KA, Eltze S, Mastroeni P, Pickard D, Dougan G, Chatfield SN, Brennan FR

Microscience Limited, 545 Eskdale Road, Winnersh Triangle, Wokingham, RG41 5TU, Berkshire, UK

[Medline record in process]
 

The S. typhimurium strain (TML DeltaaroC DeltassaV) WT05, harbouring defined deletions in genes involved in both the aromatic biosynthesis pathway (aroC) and the Salmonella Pathogenicity Island-2 (SPI-2) (ssaV) was shown to be significantly attenuated in C57 BL/6 interferon gamma knockout mice following oral inoculation. Similarly, the S. typhi strain (Ty2 DeltaaroC DeltassaV) ZH9 harbouring the aroC and ssaV mutations propagated less efficiently than wild type in human macrophages. These studies demonstrated the attractive safety profile of the aroC ssaV mutant combination. Strains S. typhimurium (TML DeltaaroC DeltassaV ) WT05 and S. typhi (Ty2 DeltaaroC DeltassaV) ZH9 were subsequently tested as vaccine vectors to deliver E. coli heat-labile toxin (LT-B) mucosally to mice. Mice inoculated orally with S. typhimurium (TML DeltaaroC DeltassaV) WT05 expressing LT-B (WT05/LT-B) elicited high titres of both LT-specific serum IgG and intestinal IgA, although no specific IgA was detected in the vagina. Similarly, intranasal inoculation of mice with S. typhi (Ty2 DeltaaroC DeltassaV) ZH9 expressing LT-B (ZH9/LT-B) elicited even higher titres of LT-specific serum antibody as well as LT-specific Ig in the vagina. We conclude that DeltaaroC DeltassaV strains of Salmonella are highly attenuated and are promising candidates both as human typhoid vaccines and as vaccine vectors for the delivery of heterologous antigens.

PMID: 12531654, UI: 22420242

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Vaccine 2003 Jan 17;21(5-6):532-7
 

Vaccine efficacy of the attenuated Erysipelothrix rhusiopathiae YS-19 expressing a recombinant protein of Mycoplasma hyopneumoniae P97 adhesin against mycoplasmal pneumonia of swine.

Shimoji Y, Oishi E, Muneta Y, Nosaka H, Mori Y

National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, 305-0856, Ibaraki, Japan

[Medline record in process]
 

The attenuated Erysipelothrix rhusiopathiae YS-19 strain was constructed for the purpose of delivering the C-terminal portion of the Mycoplasma hyopneumoniae P97 adhesin to the mucosal surface of the respiratory tract of pigs. In this study, the efficacy of the YS-19 vaccine against mycoplasmal pneumonia of swine was evaluated. Animal experiments revealed that intranasal immunization of pigs with the YS-19 strain significantly reduced the severity of pneumonic lung lesions caused by M. hyopneumoniae infection. In YS-19-immunized pigs, P97-specific serum antibodies were not detected. However, when stimulated with the P97 protein, peripheral blood mononuclear cells from the YS-19-immunized pigs had a significantly higher stimulation index (P<0.05) than that of cells from control pigs at 7 days post-challenge.

PMID: 12531653, UI: 22420241

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Vaccine 2003 Jan 17;21(5-6):521-31
 

Comparison of the antitumor efficacies of Her-2/neu DNA vaccines inducing contrasting IgG immunity but comparable CTL activity in mice.

Lee JY, Kim DH, Chung Y, Shin SU, Kang CY

Laboratory of Immunology, College of Pharmacy, Seoul National University, Shillim-Dong, Kwanak-Gu, 151-742, Seoul, South Korea

[Medline record in process]
 

The relative importance of CTL and antibodies in rejecting Her-2/neu-expressing tumors was evaluated in preventive and therapeutic models by DNA vaccination. Four human Her-2/neu-expressing plasmids (pNeu(TM), pNeu(ECD), pNeu(TM-gDs), and pNeu(ECD-gDs)) were generated encoding either the transmembrane and extracellular domains or the extracellular domain. Interestingly, these plasmids demonstrated substantial difference in inducing Her-2/neu-specific serum IgG according to their signal sequence when injected in BALB/c mice. pNeu(TM) and pNeu(ECD) induced high serum IgG titers. pNeu(TM-gDs) and pNeu(ECD-gDs) induced low or very low serum IgG titers, respectively. As a result, mice vaccinated with not only pNeu(ECD) but also pNeu(ECD-gDs) exhibited complete eradication of a small number of tumor cells. Nevertheless, when the number of tumor cells was increased in a therapeutic model, only pNeu(ECD) exhibited statistically significant antitumor immunity. These studies demonstrate that strong CTL may be sufficient in tumor prevention, but the collaboration of CTL and antibody may be required in tumor therapy.

PMID: 12531652, UI: 22420240

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Vaccine 2003 Jan 17;21(5-6):514-20
 

A mucosally administered recombinant fusion protein vaccine against schistosomiasis protecting against immunopathology and infection.

Lebens M, Sun JB, Sadeghi H, Backstrom M, Olsson I, Mielcarek N, Li BL, Capron A, Czerkinsky C, Holmgren J

Department of Medical Microbiology and Immunology, Goteborg University and the Goteborg University Research Institute, Guldhedsgatan 10A, SE-413 46, Goteborg, Sweden

[Medline record in process]
 

We have constructed and efficiently produced and purified a candidate vaccine against schistosomiasis consisting of a novel hybrid protein in which two dominant T- and B-cell epitopes from Schistosoma mansoni 28kDa glutathione-S-transferase (Sm28GST) antigen (a.a 24-43 and 191-212) are fused to cholera toxin B subunit (CTB). Intranasal treatment of S. mansoni-infected mice with the hybrid protein, which similar to native CTB was assembled into receptor binding pentamers, significantly reduced total worm burden and liver egg counts due to the induction of Sm28GST-specific antibodies. Immunopathologic granuloma formation in the liver was also significantly suppressed and there was an almost complete suppression of delayed-type hypersensitivity reactions to both Sm28GST and to total soluble egg antigen in infected animals. The results suggest that this type of hybrid protein could be used as a combined anti-immunopathology and anti-infection vaccine against schistosomiasis.

PMID: 12531651, UI: 22420239

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Vaccine 2003 Jan 17;21(5-6):507-13
 

DNA vaccination with plasmids containing various fragments of large segment genome of infectious bursal disease virus.

Chang HC, Lin TL, Wu CC

Department of Veterinary Pathobiology, 1175 ADDL, Purdue University, 47907, West Lafayette, IN, USA

[Medline record in process]
 

The present study was undertaken to determine the effectiveness in including VP2 gene of the large segment genome of infectious bursal disease virus (IBDV) in the DNA vaccine for protection of chickens against infectious bursal disease (IBD). Different fragments of the large segment gene of IBDV standard challenge (STC) strain were successfully amplified by reverse transcription-polymerase chain reaction (RT-PCR) followed by cloning into a eukaryotic expression plasmid vector (pCR3.1) as DNA vaccines. Transient expression of the encoded genes from various constructed plasmids was characterized in COS-7 cells by positive immunofluorescent staining with polyclonal or monoclonal antibody to IBDV. Chickens (1-day old) were intramuscularly injected with the individual plasmid three times at weekly intervals, challenged with IBDV strain STC at 21-day old, and observed for 10 days. Chickens receiving the plasmids containing VP2 genes, including VP243, VP24, or VP2 fragment, did not have clinical signs, mortality, and bursal atrophy and were effectively protected against IBDV infection. On the contrary, chickens receiving plasmids without containing VP2 genes, including VP4, VP3, or VP43 fragment, had marked bursal atrophy and were not protected against IBD. Antigen detection was correlated with protection; chickens protected from IBDV infection had undetectable IBDV antigen in bursae. Enzyme-linked immunosorbent assay (ELISA) antibody titer to IBDV was low or undetectable prior to or after challenge with IBDV in protected chickens receiving the plasmids containing the VP2 gene. The results indicate that inclusion of VP2 gene in the plasmid DNA is essential in achieving effective protection mediated by DNA vaccination against IBDV infection in chickens.

PMID: 12531650, UI: 22420238

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Vaccine 2003 Jan 17;21(5-6):479-84
 

Difficulties in measles elimination: prevalence of measles antibodies before and after mass vaccination campaign in Laos.

Kuroiwa C, Xayyavong P, Vongphrachanh P, Khampapongpane B, Yamanaka M, Nakamura S

Bureau of International Cooperation, International Medical Center of Japan, Tokyo, Japan

[Medline record in process]
 

Responding to the declaration of regional polio eradication in 2000, Western Pacific Region (WPR) has been strengthening the efforts for measles elimination. Nevertheless, we questioned the feasibility of the measles elimination in Laos, where measles was still endemic. This study was undertaken with the aim to examine the impact of mass measles vaccination campaign, by comparing the prevalence of measles antibodies between before and after the campaign in 2000, among the children aged 9 months to 4 years in the two pilot sites. The constraints of mass vaccination campaign have been explored in this study. It was also suggested that more efforts should be put on reconstruction of the existing routine immunization service in Laos, which had been weakened by aggressive eradication programme.

PMID: 12531647, UI: 22420235

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Vaccine 2003 Jan 17;21(5-6):473-8
 

Measles vaccine efficacy during an epidemic in 1998 in the highly vaccinated population of Poland.

Janaszek W, Gay NJ, Gut W

Department of Sera and Vaccine Evaluation, National Institute of Hygiene, Chocimska 24, Warsaw, Poland

[Medline record in process]
 

A measles epidemic with 2255 reported cases occurred in Poland between November 1997 and July 1998, despite high vaccination coverage since the 1980s. Cases occurred at all ages less than 30 years but showed two distinct peaks: young, unvaccinated children born in 1996-1997 and once vaccinated young adults born 1976-1982. The 60% of cases were among persons aged 15 years or more. A cohort study was used to investigate measles vaccine efficacy. The efficacy of a single dose of vaccine exceeded 90% and the efficacy of two doses exceeded 99% in all age-groups. These results demonstrate both the high efficacy of the monovalent measles vaccines used in Poland and the benefit of a second dose of vaccine.

PMID: 12531646, UI: 22420234

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Vaccine 2003 Jan 17;21(5-6):419-30
 

Memory T cells and vaccines.

Esser MT, Marchese RD, Kierstead LS, Tussey LG, Wang F, Chirmule N, Washabaugh MW

Clinical Assay Research and Development, MRL-Wayne, 466 Devon Park Drive, 19087-8630, Wayne, PA, USA

[Medline record in process]
 

T lymphocytes play a central role in the generation of a protective immune response in many microbial infections. After immunization, dendritic cells take up microbial antigens and traffic to draining lymph nodes where they present processed antigens to nai;ve T cells. These nai;ve T cells are stimulated to proliferate and differentiate into effector and memory T cells. Activated, effector and memory T cells provide B cell help in the lymph nodes and traffic to sites of infection where they secrete anti-microbial cytokines and kill infected cells. At least two types of memory cells have been defined in humans based on their functional and migratory properties. T central-memory (T(CM)) cells are found predominantly in lymphoid organs and can not be immediately activated, whereas T effector-memory (T(EM)) cells are found predominantly in peripheral tissue and sites of inflammation and exhibit rapid effector function. Most currently licensed vaccines induce antibody responses capable of mediating long-term protection against lytic viruses such as influenza and small pox. In contrast, vaccines against chronic pathogens that require cell-mediated immune responses to control, such as malaria, Mycobacterium tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis C virus (HCV), are currently not available or are ineffective. Understanding the mechanisms by which long-lived cellular immune responses are generated following vaccination should facilitate the development of safe and effective vaccines against these emerging diseases. Here, we review the current literature with respect to memory T cells and their implications to vaccine development.

PMID: 12531640, UI: 22420228

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Vaccine 2003 Jan 17;21(5-6):401-18
 

Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors.

Pasetti MF, Levine MM, Sztein MB

Center for Vaccine Development, University of Maryland School of Medicine, Room 480, 685 West Baltimore Street, 21201, Baltimore, MD, USA

[Medline record in process]
 

Attenuated Salmonella enterica serovar Typhi (S. Typhi) strains can serve as safe and effective oral vaccines to prevent typhoid fever and as live vectors to deliver foreign antigens to the immune system, either by the bacteria expressing antigens through prokaryotic expression plasmids or by delivering foreign genes carried on eukaryotic expression systems (DNA vaccines). The practical utility of such live vector vaccines relies on achieving a proper balance between minimizing the vaccine's reactogenicity and maximizing its immunogenicity. To advance to clinical trials, vaccine candidates need to be pre-clinically evaluated in relevant animal models that attempt to predict what their safety and immunogenicity profile will be when administered to humans. Since S. Typhi is a human-restricted pathogen, a major obstacle that has impeded the progress of vaccine development has been the shortcomings of the animal models available to assess vaccine candidates. In this review, we summarize the usefulness of animal models in the assessment of the degree of attenuation and immunogenicity of novel attenuated S. Typhi strains as vaccine candidates for the prevention of typhoid fever and as live vectors in humans.

PMID: 12531639, UI: 22420227

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Vaccine 2003 Jan 17;21(5-6):393-8
 

The information network of senior citizens in Geneva, Switzerland, and progress in flu vaccination coverage between 1991 and 2000.

Toscani L, Gauthey L, Robert CF

Department of Community Medicine, Cantonal University Hospital, Geneva University Hospital, 24 r., Micheli-du-Crest, 1211 Pascal-Eric Gaberel Analyses, 4, Geneva, Switzerland

[Medline record in process]
 

Switzerland has lagged behind other industrialized countries in increasing vaccination coverage against flu in the elderly population. The information campaign "United against Flu", started in Geneva in 1993, gradually extended to other French and Italian speaking cantons in Switzerland and indirectly affected German-speaking cantons. Activities developed include the production of TV spots, press conferences, information forwarded to health professionals, an Internet site and information material such as leaflets and posters to risk groups. The campaign is evaluated by repeated surveys that measure vaccination coverage as well as network of informants, knowledge and perceptions in the geriatric population. Vaccination coverage of the geriatric population in Geneva canton has increased from 29% in 1991 to 59% in the year 2000.

PMID: 12531637, UI: 22420225

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Vaccine 2003 Jan 17;21(5-6):376-385
 

A modified cholera holotoxin CT-E29H enhances systemic and mucosal immune responses to recombinant Norwalk virus-virus like particle vaccine.

Periwal SB, Kourie KR, Ramachandaran N, Blakeney SJ, DeBruin S, Zhu D, Zamb TJ, Smith L, Udem S, Eldridge JH, Shroff KE, Reilly PA

Department of Viral Vaccine Immunology, Wyeth-Ayerst Research, 10965, Pearl River, NY, USA

[Record supplied by publisher]
 

In this study, we evaluated the potential of a genetically modified cholera toxin, CT-E29H as an adjuvant for recombinant Norwalk virus like particle (NV-VLP) vaccine. This detoxified mutant, containing E to H substitution at amino acid 29 of the CT-A1 subunit, was administered with a recombinant Norwalk virus like particle vaccine to Balb/c mice by mucosal routes to monitor the induction of mucosal, humoral and cellular responses. We observed that a low dose of NV-VLP (5&mgr;g) with the adjuvant delivered by the intranasal route (IN) was more effective than the highest dose (200&mgr;g) delivered by oral route at inducing both cellular and NV-VLP specific IgG and IgA responses. Higher counts of antigen specific IgA secreting cells were observed in the Peyer's Patches (PP) following delivery of the vaccine with CT-E29H as compared to delivery of vaccine by mucosal routes without CT-E29H. Furthermore, there was an increase in antigen specific cells producing IL-4 from animals that received the vaccine with the adjuvant. Delivery of the vaccine by the oral route results in antigen specific CD4(+) and CD8(+) T cells in PP and spleen. Addition of CT-E29H results in an increase of antigen specific CD4(+) cell population in PP and both CD4(+) and CD8(+) populations in the spleen. These cellular and cytokine responses suggest that combining the vaccine with CT-E29H results in a stronger Th2 type response. Collectively, these results indicate that immune responses to NV-VLP vaccine are qualitatively and quantitatively improved when the vaccine is delivered along with CT-E29H, and thus merits its further consideration as a mucosal adjuvant.

PMID: 12531635

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Vaccine 2003 Jan 17;21(5-6):368-75
 

Immunogenicity and protective efficacy of a formalin-inactivated rotavirus vaccine combined with lipid adjuvants.

Johansen K, Schroder U, Svensson L

Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, S-171 82, Solna, Sweden

[Medline record in process]
 

The immunogenicity and protective efficacy of inactivated rotavirus vaccine administered intramuscularly with lipid adjuvants; MPL((R)) (monophosphoryl lipid A from Salmonella minnesota) or L3((R)) (monooleate/lauric acid) was evaluated in an infant mouse model. Purified and formalin-inactivated rhesus rotavirus (I-RRV) combined with one of the adjuvants were administered to female balb/c mice at 0, 4 and 8 weeks. High serum IgG antibody titers developed in all vaccinated groups; I-RRV (GMT 45,524+/-9,819), I-RRV-MPL((R)) (GMT 190,637+/-64,250) and I-RRV-L3((R)) (GMT 126,266+/-27,553). The formalin-inactivation procedure preserved neutralizing epitopes and elicited high neutralizing antibody titers; I-RRV (GMT 43,053 S.E.M.+/-4,189), I-RRV-MPL((R)) (GMT 66,398 S.E.M.+/-20,202) and I-RRV-L3((R)) (GMT 60,887 S.E.M.+/-10,750). All offsprings to immunized dams were protected against clinical diarrhea upon oral challenge with RRV. The IgG1/IgG2a ratio was in all immunized groups approximately 1 suggesting development of a balanced Th1/Th2 response.

PMID: 12531634, UI: 22420222

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Vaccine 2003 Jan 17;21(5-6):354-60
 

Anticipating rotavirus vaccines: epidemiology and surveillance of rotavirus in South Africa.

Steele AD, Peenze I, de Beer MC, Pager CT, Yeats J, Potgieter N, Ramsaroop U, Page NA, Mitchell JO, Geyer A, Bos P, Alexander JJ

MRC/MEDUNSA Diarrhoeal Pathogens Research Unit, P.O. Box 173, MEDUNSA 0204, Pretoria, South Africa

[Medline record in process]
 

Rotavirus infection is associated with acute infantile gastroenteritis in infants and young children globally. In South Africa, rotavirus infection has been shown to be associated with approximately one-quarter of all diarrhoeal admissions to hospital. Rotavirus infection predominantly occurs in infants less than 12 months of age (75%) and has a peak of shedding during the cooler, drier months of the year. A secondary peak during the spring has been observed. Multiple infections with rotavirus and at least one other microbial agent are common. The circulating VP7 serotypes and VP4 genotypes have been determined in various regions of South Africa and show a geographic specific distribution. A decade previously, P[8]G1 or G4 strains predominated, and P[4]G2 strains occurred in an epidemic pattern in one region. More recently, rotavirus strains with P[6] genotype have become common and novel VP7/VP4 genotype combinations are occurring across the country. G9 strains have been reported from Cape Town to Vendaland. The circulating rotavirus types observed in this study add to the knowledge of the natural history of rotavirus infection and provide the groundwork to consider future vaccine strategies.

PMID: 12531632, UI: 22420220

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Vaccine 2003 Jan 17;21(5-6):347-53
 

Prospects for a mucosally-administered vaccine against Helicobacter pylori.

Svennerholm AM

Department of Medical Microbiology and Immunology and Goteborg University Research Institute (GUVAX), Goteborg University, P.O. Box 435, 40530, Goteborg, Sweden

[Medline record in process]
 

PMID: 12531631, UI: 22420219

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Vaccine 2003 Jan 17;21(5-6):333-40
 

Immune responses elicited against multiple enterotoxigenic Escherichia coli fimbriae and mutant LT expressed in attenuated Shigella vaccine strains.

Barry EM, Altboum Z, Losonsky G, Levine MM

Center for Vaccine Development, University of Maryland, 685 West Baltimore Street, 21201, Baltimore, MD, USA

[Medline record in process]
 

Shigella and enterotoxigenic Escherichia coli (ETEC) continue to be important causes of diarrheal disease in infants and young children in developing countries and are major etiologic agents of traveler's diarrhea. Since attenuated strains of Shigella have been developed as live oral vaccines against shigellosis, we have adapted these attenuated Shigella strains to serve as carriers of ETEC antigens, thereby constituting a hybrid vaccine. Since protective immunity against ETEC is largely directed against fimbrial antigens (of which there are multiple antigenic types), we have individually expressed four different ETEC fimbriae, including CFA/I, CS2, CS3, and CS4, using DeltaguaBA attenuated Shigella vaccine strain CVD 1204 as a prototype live vector. Following mucosal (intranasal) immunization of guinea pigs, serum IgG and mucosal IgA responses were elicited against each fimbrial type. An additional strain was constructed expressing a detoxified version of the human ETEC variant of heat labile toxin (LThK63). Following mucosal immunization of guinea pigs with a mixed inoculum containing five Shigella strains each expressing a different ETEC antigen, immune responses were observed against each ETEC antigen plus the Shigella vector.

PMID: 12531629, UI: 22420217

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Vaccine 2003 Jan 30;21(7-8):816-9
 

Immunogenic measles antigens expressed in plants: role as an edible vaccine for adults.

Muller CP, Fack F, Damien B, Bouche FB

Department of Immunology and WHO Collaborative Center for Measles, Laboratoire National de Sante, P.O. Box 1102, 20A rue Auguste Lumiere, L-1950, Luxembourg, Luxembourg

[Medline record in process]
 

Vaccine-induced immunity against measles is less robust than natural immunity. Waning of immunity in vaccines may eventually require a revaccination of adults. Measles antigens expressed in plants have been shown to be antigenic and immunogenic both after invasive and oral vaccination. Strategies for the vaccination of adults, the potential of an oral measles vaccine produced in edible plants and the design of suitable antigens are discussed.

PMID: 12531367, UI: 22420294

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Vaccine 2003 Jan 30;21(7-8):812-5
 

Corn as a production system for human and animal vaccines.

Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, Lamphear BJ, Drees CF, Jilka JM, Hood EE, Howard JA

ProdiGene, 101 Gateway Boulevard, Suite 100, 77845, College Station, TX, USA

[Medline record in process]
 

The synthesis of selected antigens in plants and their oral delivery has great potential for reducing the costs of vaccine production and administration. The application of this technology requires antigen concentrations in final plant material to be uniform to ensure consistent dosing. In addition, antigen levels should be such as to allow the volume of each dose, containing a set amount of antigen, to be practical for oral delivery. Here, we demonstrate that the Lt-B protein of enterotoxigenic E. coli is evenly distributed in defatted corn germ prepared from transgenic grain. Furthermore, the choice of sub-cellular location for Lt-B affects accumulation of the protein in excess of four orders of magnitude.

PMID: 12531366, UI: 22420293

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Vaccine 2003 Jan 30;21(7-8):809-11
 

Targeting of plant-derived vaccine antigens to immunoresponsive mucosal sites.

Rigano MM, Sala F, Arntzen CJ, Walmsley AM

Department of Plant Biology, Arizona State University, 85215, Tempe, AZ, USA

[Medline record in process]
 

Most pathogenic microorganisms enter their host via the mucosal surfaces lining the digestive, respiratory and urino-reproductive tracts of the body. The most efficient means of protecting these surfaces is through mucosal immunization. Transgenic plants are safe and inexpensive vehicles to produce and mucosally deliver protective antigens. However, the application of this technology is limited by the poor response of the immune system to non-particulate, subunit vaccines. Co-delivery of therapeutic proteins with targeting proteins, such as the B subunit of the Escherichia coli heat labile enterotoxin (LTB), could increase the effectiveness of such antigens.

PMID: 12531365, UI: 22420292

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Vaccine 2003 Jan 30;21(7-8):803-8
 

Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives.

Sala F, Manuela Rigano M, Barbante A, Basso B, Walmsley AM, Castiglione S

Department of Biology, University of Milano, Via Celoria 26, 20133, Milano, Italy

[Medline record in process]
 

Stable integration of a gene into the plant nuclear or chloroplast genome can transform higher plants (e.g. tobacco, potato, tomato, banana) into bioreactors for the production of subunit vaccines for oral or parental administration. This can also be achieved by using recombinant plant viruses as transient expression vectors in infected plants. The use of plant-derived vaccines may overcome some of the major problems encountered with traditional vaccination against infectious diseases, autoimmune diseases and tumours. They also offer a convenient tool against the threat of bio-terrorism. State of the art, experimental strategies, safety and perspectives are discussed in this article.

PMID: 12531364, UI: 22420291

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Vaccine 2003 Jan 30;21(7-8):795-7
 

Contribution of dead cells to the immunogenicity of an autologous, hapten-modified melanoma vaccine.

Berd D

Department of Medicine, Division of Medical Oncology of Thomas Jefferson University, 1015 Walnut Street, Suite 1024, 19107, Philadelphia, PA, USA

[Medline record in process]
 

We have reported that treatment of melanoma patients with a vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), induced delayed-type hypersensitivity (DTH) to autologous, unmodified tumor cells. Moreover, this response was a significant and independent predictor of survival. We analyzed the vaccines prepared for 284 patients who were treated following resection of regional or distant metastases to determine whether the dose and composition correlated with immunological response. Regression analysis showed no significant association between the magnitude of this DTH response and the number of live (trypan blue-excluding) melanoma cells per dose. In fact, vaccines containing higher numbers or higher proportions of dead, but intact, tumor cells induced larger DTH responses to autologous unmodified tumor. The observation that dead tumor cells are immunogenic may be applicable to other cellular human cancer vaccines and underscores the need for applying pharmacological principles to cancer immunotherapy.

PMID: 12531362, UI: 22420289

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Vaccine 2003 Jan 30;21(7-8):776-80
 

Immunity under the skin: potential application for topical delivery of vaccines.

Partidos CD, Beignon AS, Mawas F, Belliard G, Briand JP, Muller S

UPR 9021, CNRS, Immunologie et Chimie Therapeutiques, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F-67084, Strasbourg, France

[Medline record in process]
 

With the technological advances in biomedical sciences and the better understanding of how the immune system works, new immunisation strategies and vaccine delivery options, such sprays, patches, and edible formulations have been developed. This has opened up the possibility of administering vaccines without the use of needles and syringes. Already topical immunisation is a reality and it has the potential to make vaccine delivery more equitable, safer, and efficient. Furthermore, it would increase the rate of vaccine compliance and greatly facilitate the successful implementation of worldwide mass vaccination campaigns against infectious diseases. This review gives a brief account of the latest developments of application of candidate vaccine antigens onto bare skin and describes some of our recent observations using peptide and glycoconjugate vaccines as immunogens.

PMID: 12531358, UI: 22420285

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Vaccine 2003 Jan 30;21(7-8):746-52
 

Protection against murine listeriosis by oral vaccination with recombinant Salmonella expressing protective listerial epitopes within a surface-exposed loop of the TolC-protein.

Spreng S, Dietrich G, Goebel W, Gentschev I

Department of Microbiology, University of Wurzburg, D-97074, Wurzburg, Germany

[Medline record in process]
 

Based on the topology of the outer membrane protein TolC of Escherichia coli, a new plasmid-encoded system was created which allows the expression of antigenic peptides within permissive, surface-exposed domains of TolC. To assess the capacity of this novel antigen display system, a protective CD4 T-cell epitope of the p60 protein of Listeria monocytogenes was inserted within an extracellular loop of the TolC-protein and expressed in surface-exposed form by attenuated Salmonella enteritidis. Mice immunized orally with this recombinant S. enteritidis live vaccine strain were protected against a lethal challenge with wildtype L. monocytogenes.

PMID: 12531354, UI: 22420281

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Vaccine 2003 Jan 30;21(7-8):742-745
 

Tolerability of modified tick-borne encephalitis vaccine FSME-IMMUN "NEW" in children: results of post-marketing surveillance.

Pavlova BG, Loew-Baselli A, Fritsch S, Poellabauer EM, Vartian N, Rinke I, Ehrlich HJ

Baxter BioScience Vaccines, Clinical Development and Medical Affairs, Industriestr. 67, A-1221, Vienna, Austria

[Record supplied by publisher]
 

A new, highly purified, inactivated tick-borne encephalitis (TBE) vaccine FSME-IMMUN "NEW" has been developed by Baxter using a production virus seed derived from chick embryo cells instead of mouse brain. In clinical trials, the vaccine was shown to be highly immunogenic and well tolerated in adults and children. Following licensure in 2001, the tolerability of half the adult dose of FSME-IMMUN "NEW" (1.2&mgr;g antigen/0.25ml) was investigated in a post-marketing surveillance in 1899 children aged 6 months to 12 years. Rectal body temperature was measured daily for 3 days after the first vaccination. An overall fever rate of 20.3% (95% CI=18.5; 22%) was observed, which was mostly mild in nature (>38.0 to </=39.0 degrees C) with only 0.3% (95% CI=0.1; 0.6%) severe cases reported. The highest fever rates were reported in February and March (when febrile illnesses are common) and in the 1-3 years age group (63% of the total surveillance population). These results demonstrated that, in routine medical practice, FSME-IMMUN "NEW" vaccine at a dose of 1.2&mgr;g antigen/0.25ml is safe for the first vaccination in children.

PMID: 12531353

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Vaccine 2003 Jan 30;21(7-8):738-41
 

Clinical evaluation of a polygeline-free tick-borne encephalitis vaccine for adolescents and adults.

Zent O, Beran J, Jilg W, Mach T, Banzhoff A

Chiron Vaccines, Marburg, Germany

[Medline record in process]
 

OBJECTIVE: To evaluate immunogenicity and safety of a polygeline-free tick-born encephalitis (TBE) vaccine in a clinical program. METHOD: A total of 3118 subjects aged 12-76 years were enrolled in three clinical trials. The clinical studies were conducted in 15 centers in three European countries. Evidence of neutralizing TBE antibodies was used as surrogate parameter for efficacy assessment. RESULTS: All subjects analyzed achieved levels of TBE antibodies postimmunization to fulfill the definition of seroconversion or a four-fold increase. The new TBE vaccine appeared to be well tolerated by subjects. Only very few febrile reactions, mainly 38.5 degrees C were reported. No serious or unexpected adverse events related to vaccination were reported. CONCLUSION: These successful results in terms of both immunogenicity and safety indicate that the TBE vaccination with this polygeline-free TBE vaccine can be used safely in adolescents and adults.

PMID: 12531352, UI: 22420279

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Vaccine 2003 Jan 30;21(7-8):734-7
 

Serum bactericidal activity correlates with the vaccine efficacy of outer membrane vesicle vaccines against Neisseria meningitidis serogroup B disease.

Holst J, Feiring B, Fuglesang JE, Hoiby EA, Nokleby H, Aaberge IS, Rosenqvist E

Division of Infectious Disease Control, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, N-0403, Oslo, Norway

[Medline record in process]
 

For evaluation of serum bactericidal activity (SBA) as surrogate for the efficacy of outer membrane vesicle (OMV) vaccines against Neisseria meningitidis serogroup B disease, we have reanalyzed data from a randomized double blind placebo-controlled efficacy trial involving 172,000 secondary school students (aged 13-14 years) in Norway (1988-1991). A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies. An efficacy of 87% was calculated for a 10-month observation period. However, after an observation period of 29 months, the estimated efficacy against group B disease induced by vaccination was 57%. The immunogenicity study showed that the SBA geometric mean titer (GMT) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose. One year after vaccination the GMT was reduced to 2.8. A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose (i.e. when cases of disease started to appear) a strong booster response was induced. Ten months after the second dose the SBA was reduced to near pre-immunization level. Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3. One year after the third dose, the GMT was markedly higher than 6 weeks after the second dose (12.6 versus 8.8). Thus, protection after vaccination corresponds with the level of SBA. In order to reach lasting protective levels of SBA in a population, three vaccine doses are probably required. Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines.

PMID: 12531351, UI: 22420278

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Vaccine 2003 Jan 30;21(7-8):729-733
 

Dramatic decline of serogroup C meningococcal disease in Catalonia (Spain) after a mass vaccination campaign with meningococcal C conjugated vaccine.

Salleras L, Domi;nguez A, Cardenosa N

Directorate of Public Health, Department of Health and Social Security, Generalitat of Catalonia, Travessera de les Corts, 131-159 Pavello Ave Maria, 08028, Barcelona, Spain

[Record supplied by publisher]
 

In the last quarter of the year 2000, the meningococcal C conjugated vaccine was incorporated into the routine vaccination schedule in Catalonia (at 2, 4 and 6 months). In addition a vaccination campaign was carried out in children <6 years of age, with a coverage of 96.2%. The effectiveness of the vaccination in this age group during 2001 and the first 28 weeks of 2002 was 100% (94.27-100%). A vaccination campaign has been carried out in 6-19-year olds during 2001 and 2002, with a coverage rate of 23.5% in the year 2001. In this age group a reduction in disease incidence was seen in the 2000-2001 season, but not in the following one.

PMID: 12531350

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Vaccine 2003 Jan 30;21(7-8):725-728
 

Impact of mass vaccination with polysaccharide conjugate vaccine against serogroup C meningococcal disease in Spain.

Salleras L, Domi;nguez A, Cardenosa N

Department of Health and Social Security, Directorate of Public Health, Travessera de les Corts, 131-159 Pavello Ave Maria, 08028, Barcelona, Spain

[Record supplied by publisher]
 

During the fourth quarter of 1997, a vaccination campaign using the meningococcal C polysaccharide vaccine was carried out in 14 autonomous regions of Spain. The remaining three regions did not participate. In the last quarter of the year 2000, a mass vaccination campaign using the meningococcal C conjugated vaccine was carried out in all regions. In the year 2001 the incidence decreased in all regions, although the decrease was greater in regions that did not vaccinate in 1997. In contrast, case fatality rates did not decrease. During 2001, the incidence rate of meningococcal C disease was still lower (0.32 per 100,000 persons-year) in the regions that vaccinated in 1997 with the polysaccharide vaccine than in those that did not (0.64 per 100,000 persons-year).

PMID: 12531349

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Vaccine 2003 Jan 30;21(7-8):721-4
 

Options for improvement of the Dutch measles vaccination schedule.

van den Hof S, Wallinga J, Widdowson MA, Conyn-van Spaendonck MA

Department of Infectious Diseases Epidemiology, National Institute for Public Health and The Environment, P.O. Box 1, BA 3720, Bilthoven, The Netherlands

[Medline record in process]
 

We investigated which vaccination schedule gives best protection to the vaccinating population, in case of a measles epidemic in pockets of unvaccinated individuals. We explored the effect of an additional measles vaccination (at 6 or 9 months), advancing the first measles-mumps-rubella (MMR) vaccination from 14 to 11 months, and advancing the second MMR from 9 to 4 years. Measures of protection among vaccinees (percentage of susceptibles, number of reported cases, percentage of lifetime spent susceptible) were estimated with a mathematical model of the impact of antibody level on seroconversion and immunity. Advancing the age of second MMR vaccination prevents considerably more cases among vaccinees than an extra early measles vaccination or advancing the age of first MMR vaccination.

PMID: 12531348, UI: 22420275

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Vaccine 2003 Jan 30;21(7-8):698-701
 

Effectiveness of a mass hepatitis A vaccination program in preadolescents.

Domi;nguez A, Salleras L, Carmona G, Batalla J

Department of Health and Social Security, General Directorate of Public Health, Generalitat of Catalonia, Travessera de les Corts, 131-159, 08028, Barcelona, Spain

[Record supplied by publisher]
 

A program of mass hepatitis A+B vaccination in preadolescents in schools was begun in the Catalonia in the last quarter of 1998. This study investigated the impact of the program by comparing the incidence of hepatitis A in vaccinated and unvaccinated cohort.The greatest reduction of the incidence rate of hepatitis A was observed in the 10-14 years age group, from 10.3 per 100,000 persons-year in the period 1996-1998 to 1.8 per 100,000 persons-year in the period 1999-2001. The global incidence decreased from 6.2 to 2.6 per 100,000 persons-year.After analysis of cases occurring in the vaccinated and non vaccinated cohort, the effectiveness of the vaccination program was estimated at 97.0% (95% CI: 78.6-99.6).

PMID: 12531343

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Vaccine 2003 Jan 30;21(7-8):696-7
 

Vaccination strategies against hepatitis A in southern Europe.

Franco E, Vitiello G

Department of Public Health, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy

[Medline record in process]
 

Hepatitis A virus (HAV) infection is decreasing in southern European countries, where epidemiological conditions vary among regions depending on the social and health-care system development. In high endemic settings, HAV infection has not heavy social and economic weight while in countries with a moderate/low degree of endemia there is a call for targeted vaccination policy. In countries, like Spain and in Italy, where several studies confirm an increase in susceptible adults, vaccination strategies have been applied and recommendations have been published about hepatitis A prevention. Universal hepatitis A immunization seems economically unattractive and most evidences for targeted vaccination have not yet been sufficiently investigated. Vaccine should be used to protect travellers to countries where HAV infection is a major risk and in preventing secondary cases and outbreaks.

PMID: 12531342, UI: 22420269

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Vaccine 2003 Jan 30;21(7-8):685-91
 

Impact of universal vaccination programmes on the epidemiology of hepatitis B: 10 years of experience in Italy.

Bonanni P, Pesavento G, Bechini A, Tiscione E, Mannelli F, Benucci C, Nostro AL

Public Health Department, University of Florence, Viale G.B. Morgagni 48, 50134, Florence, Italy

[Medline record in process]
 

Ten years have elapsed since routine vaccination of infants and of 12-year-old adolescent was implemented in Italy.In this period, evidence has accumulated on the epidemiological impact of universal immunisation.Coverage is on average >90% and is >/=95% in many areas of the country. Incidence of acute hepatitis B, that was already declining before 1991, was further decreased by routine vaccination programmes.This is particularly evident in adolescents and young adults (cohorts involved by mandatory vaccination), while incidence shows little changes in older subjects according to data of the last years. Prevalence of hepatitis B virus (HBV) markers detected by sero-epidemiological studies on anonymous sera confirms both the very high coverage with hepatitis B vaccination and the virtual absence of chronic HBsAg carriers in cohorts involved by routine vaccination programmes. The system of passive surveillance on adverse events following hepatitis B vaccination supports the excellent safety record of hepatitis B vaccines.In a hyperendemic area of Southern Italy, where a pilot programme was firstly implemented, it was also possible to document the decline of the involvement of hepatitis B in chronic liver pathologies (from 48% in 1982 to 18% in 1997).If coverage rates are maintained at the present levels, elimination of HBV transmission in Italy may be envisaged in few decades.

PMID: 12531340, UI: 22420267

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Vaccine 2003 Jan 30;21(7-8):678-83
 

Experience with registered mucosal vaccines.

Dietrich G, Griot-Wenk M, Metcalfe IC, Lang AB, Viret JF

Berna Biotech Ltd., Rehhagstr. 79, CH-3018, Berne, Switzerland

[Medline record in process]
 

Most pathogens gain access to their host through mucosal surfaces. It is therefore desirable to develop vaccination strategies that lead to mucosal immune responses. Ideally, a vaccine should be administered mucosally in order to elicit mucosal protection. Several attenuated live viral and bacterial pathogens are registered as oral vaccines for human use, including the oral polio vaccine (Sabin) as well as attenuated strains of Salmonella typhi and Vibrio cholerae. These attenuated bacterial live vaccines-S. typhi Ty21a as well as V. cholerae CVD 103-HgR-are employed as vaccines against typhoid and cholera, respectively. In this manuscript, we review the immune responses that are induced by these vaccines, with a focus on mucosal immunity.

PMID: 12531339, UI: 22420266

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Vaccine 2003 Jan 30;21(7-8):667-70
 

Mycobacterium bovis BCG-based vaccines against tuberculosis: novel developments.

Dietrich G, Viret JF, Hess J

Berna Biotech Ltd., Bacterial Vaccine Research, Rehhagstr. 79, CH-3018, Berne, Switzerland

[Medline record in process]
 

Mycobacterium bovis Bacille Calmette-Guerin (BCG) is one of the most widely used vaccines. Modern techniques in genome manipulation allow the construction of recombinant (r)-BCG strains that can be employed as highly immunogenic vaccines against tuberculosis (TB) with an enhanced safety profile. In addition, the development of novel procedures to cultivate BCG will allow the large-scale production of future BCG-based vaccines.

PMID: 12531337, UI: 22420264

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Vaccine 2003 Jan 30;21(7-8):663-6
 

The rationale of a peptide-conjugate vaccine against measles.

Putz MM, Muller CP

Department of Immunology, Laboratoire National de Sante, P.O. Box 1102, 20A Rue Auguste Lumiere, 1950, Luxembourg, Luxembourg

[Medline record in process]
 

The live-attenuated measles vaccine is poorly immunogenic in infants because of immune suppressive maternal antibodies and immaturity of the infant's immune system. Selected peptides corresponding to sequential, subdominant B cell epitopes of measles virus (MV) glycoproteins have been shown to induce neutralizing and protective antibodies even in the presence of whole virus antibodies. Similar to polysaccharide-conjugate vaccines, which are highly effective in infants a peptide-conjugate vaccine against measles is proposed. Such a vaccine induces carrier-specific T cells, avoiding measles-specific Th2 cells associated with the risk of atypical measles. This article discusses the rationale of such a strategy and its future potential.

PMID: 12531336, UI: 22420263

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Vaccine 2003 Jan 30;21(7-8):659-62
 

Progress in DNA vaccine for prophylaxis and therapy of hepatitis B.

Thermet A, Rollier C, Zoulim F, Trepo C, Cova L

INSERM U271, 151 Cours Albert Thomas, 69003, Lyon, France

[Medline record in process]
 

Increasing lines of evidence suggest that DNA vaccine is of interest to fight chronic hepatitis B virus (HBV) infection. We used the Pekin duck infected by duck HBV (DHBV), closely related to the human virus, which is an attractive model allowing study of protective and therapeutic effectiveness of DNA vaccines against hepatitis B. Immunisation with a plasmid encoding the DHBV large (L) envelope protein induced a strong, specific, highly neutralising and long-lasting anti-preS humoral response in uninfected ducks. Importantly, maternal antibodies elicited by such DNA immunisation were vertically transmitted and protected progeny against viral challenge. Therapeutic immunisation of chronic DHBV-carrier ducks with this plasmid DNA led to the dramatic and sustained decrease in viral replication and even to clearance of intrahepatic viral covalently close circular DNA (cccDNA) pool in some animals. Our recent combination therapy data showed even a more pronounced antiviral effect of DNA vaccine to DHBV envelope protein when associated with antiviral drug (lamivudine) treatment. Therefore, DNA-based vaccine appears as a promising new approach for prophylaxis and therapy of hepatitis B.

PMID: 12531335, UI: 22420262

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Vaccine 2003 Jan 30;21(7-8):649-58
 

Induction of immune responses by DNA vaccines in large animals.

Babiuk LA, Pontarollo R, Babiuk S, Loehr B, van Drunen Littel-van den Hurk S

Veterinary Infectious Disease Organization, 120 Veterinary Road, SK, S7N 5E3, Saskatoon, Canada

[Medline record in process]
 

It is generally recognized that DNA vaccines are often less effective in large animals than in mice. One possible reason for this reduced effectiveness may be transfection deficiency and the low level of expression elicited by plasmid vectors in large animals. In our attempt to enhance transfection efficiency and, thereby, enhance immune responses, we employed a variety of methods inducing gene gun delivery or suppositories as delivery vehicles to mucosal surfaces, as well as electroporation for systemic immunization. To test these different systems, we used two different antigens-a membrane antigen from bovine herpesvirus glycoprotein (BHV-1) gD and a particulate antigen from hepatitis virus B. Gene gun and suppository delivery of BHV-1 gD to the vagina resulted in the induction of mucosal immunity not only in the vagina, but also at other mucosal surfaces. These data support the contention of a common mucosal immune system. In the case of electroporation, we were able to develop significant enhancement of gene expression following electroporation with surface electrodes (non-invasive electroporation) as well as invasive electroporation using single or six-needle electrodes. Various delivery systems such as bioject or needle delivery also influenced the immune response in both the presence and absence of electroporation. These studies also demonstrated that co-administration of plasmids coding for two different antigens (BHV-1 gD and hepatitis B surface antigen (HbsAg)) did not result in significant interference between the plasmids. These studies suggest that various combinations of delivery systems can enhance immunity to DNA-based vaccines and make them practical for administration of these vaccines in large animals.

PMID: 12531334, UI: 22420261

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Vaccine 2003 Jan 30;21(7-8):644-8
 

Immunogenicity of an HIV-1 gag DNA vaccine carried by attenuated Shigella.

Xu F, Hong M, Ulmer JB

Vaccines Research, Chiron Corporation, 4560 Horton St., mail stop 4-3, 94608, Emeryville, CA, USA

[Medline record in process]
 

The use of live attenuated invasive bacteria as a carrier for DNA-based vaccines has been reported recently. In this study, we used a Shigella flexneri serotype 2a rfbF mutant for immunization of a DNA vaccine coding for HIV-1 SF2 Gag. The recombinant bacterial vector delivered gag DNA to mammalian cells in vitro resulting in Gag protein expression, and was found to have a low level of pathogenicity among a number of Shigella cell spread defective mutants tested. Intranasal immunization of mice with live recombinant bacterial cells induced a gag-specific cellular immune response similar to that seen with i.m. injection of naked DNA. Importantly, a strong boosting effect was observed in mice primed with DNA, suggesting utility of bacterial vectors in prime-boost vaccination regimens.

PMID: 12531333, UI: 22420260

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Vaccine 2003 Jan 30;21(7-8):638-43
 

Virus-like particle and DNA-based candidate AIDS vaccines.

Yao Q, Bu Z, Vzorov A, Yang C, Compans RW

Department of Microbiology and Immunology, Emory University School of Medicine, 30322, Atlanta, GA, USA

[Medline record in process]
 

Both humoral and cellular immune responses are critical for the control of HIV infection and replication. We have established systems for production of HIV and SIV virus-like particles containing high levels of viral Env proteins using the baculovirus expression system. Evaluation of immunogenicity showed that immunization with virus-like particles induced both cellular and neutralizing antibody responses. Furthermore, mucosal administration of virus-like particles effectively induced both mucosal and systemic immune responses. These results indicate that virus-like particles consisting of HIV structural proteins are an attractive vaccine platform for eliciting anti-viral immune responses, especially neutralizing antibody responses. We have also synthesized codon-optimized genes for HIV Env proteins and evaluated their immunogenicity. Combinations of virus-like particle and DNA-based vaccination are promising for inducing strong cellular and neutralizing antibody responses against HIV.

PMID: 12531332, UI: 22420259

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Vaccine 2003 Jan 30;21(7-8):629-37
 

A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIV(mac)251 challenge in Rhesus Macaques.

Muthumani K, Bagarazzi M, Conway D, Hwang DS, Manson K, Ciccarelli R, Israel Z, Montefiori DC, Ugen K, Miller N, Kim J, Boyer J, Weiner DB

Department of Pathology and Laboratory of Medicine, University of Pennsylvania, 505 Stellar Chance Laboratories, 422 Curie Blvd., 19104, Philadelphia, PA, USA

[Medline record in process]
 

DNA vaccines are an important vaccine approach for many infectious diseases including human immunodeficiency virus (HIV). Recently, there have been exciting results reported for plasmid vaccination in pathogenic SHIV model systems. In these studies, plasmid vaccines supplemented by IL-2 Ig cytokine gene adjuvants or boosted by recombinant MVA vectors expressing relevant SIV and HIV antigens prevented CD4(+) T-cell loss and lowered viral loads following pathogenic challenge. However, similar results have not been reported in a direct pathogenic macaque challenge model. Here we report on a study of the ability of a multiplasmid SIV DNA vaccine in a pathogenic SIV251 rhesus mucosal challenge study. We observed that pGag/Pol+pEnv/Rev plasmid vaccines could not prevent SIV infection; however, vaccinated animals exhibited significant improvement in control of viral challenge compared to control animals. Furthermore, vaccinated animals exhibited protection against CD4(+) T-cell loss.

PMID: 12531331, UI: 22420258

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Vaccine 2003 Jan 30;21(7-8):624-8
 

V-1 Immunitor: oral therapeutic AIDS vaccine with prophylactic potential.

Jirathitikal V, Sooksathan P, Metadilogkul O, Bourinbaiar AS

Immunitor Corporation Co. Ltd., 71 Moo 5, Bangpakong Industrial Park, Takarm, 24130, Chachoengsao, Thailand

[Medline record in process]
 

V-1 Immunitor (V1) is a therapeutic vaccine comprising pooled HIV antigens formulated into an oral pill. Recent V1 studies demonstrated body weight gain, increase in CD4 and CD8 cells, decrease in viral load, and improved survival of end-stage AIDS patients. The potential of V1 as a prophylactic vaccine has been evaluated in a phase II placebo-controlled trial on 35 volunteers. Twenty HIV-negative volunteers who received V1 b.i.d. for 4 weeks had gained 28.2 and 17.5% in absolute CD4 (825 versus 1058; P=0.007) and CD8 (597 versus 702; P=0.013) cells, while lymphocytes in placebo group did not increase, suggesting that CD4 and CD8 counts may become an easily measurable immune correlate of the efficacy of AIDS vaccines. V1 does not appear to induce HIV-specific antibodies as orally administered immunogens usually produce cell-mediated but not systemic humoral response. V1 as a preventive oral vaccine targeting cellular and mucosal immunity deserves further evaluation.

PMID: 12531330, UI: 22420257

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Vaccine 2003 Jan 30;21(7-8):620-3
 

Therapeutic vaccination for future management of HIV/AIDS.

Lisziewicz J, Bakare N, Lori F

Research Institute for Genetic and Human Therapy (RIGHT), 2233 Wisconsin Avenue NW Suite 503, 20007, Washington, DC, USA

[Medline record in process]
 

The investigation of novel and innovative treatment approaches for long-term management of HIV-infection has intensified due to the growing number of infected individuals worldwide and the constraints of resistance, toxicity and inconvenience associated with lifelong therapy. Current treatment relies entirely on antiretroviral drugs targeting various stages of the life cycle of HIV, rather than on leveraging the immune system. However, the boosting of HIV-specific immune responses in chronic infection offers a vast potential for synergy with antiretroviral drugs, thereby contributing to durable control of viral replication. A novel immunotherapeutic agent that delivers plasmid DNA to dendritic cells after topical skin application is the first therapeutic vaccine that has demonstrated immunological and clinical benefit in chronically infected rhesus macaques in combination with antiretroviral therapy.

PMID: 12531329, UI: 22420256

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Vaccine 2003 Jan 30;21(7-8):616-9
 

Prospects and challenges for prophylactic and therapeutic HIV vaccines.

Klein M

Aventis Pasteur, Campus Merieux, 1541 Avenue Marcel Merieux, 69280, Marcy l'Etoile, France

[Medline record in process]
 

The best strategy for controlling the HIV pandemic remains the development of an efficacious prophylactic vaccine. Efficacy trials performed during this decade will yield information on the protective ability of first-generation vaccines. Several novel mixed-modality vaccines capable of inducing high-frequency CD8(+) T-cell responses in macaques are being evaluated in humans. New hope has been raised with the prospect of therapeutic HIV vaccines. However, the development of HIV vaccines remains a formidable challenge to both the industry and the scientific community.

PMID: 12531328, UI: 22420255

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Vaccine 2003 Jan 30;21(7-8):605-10
 

Two years into reverse vaccinology.

Adu-Bobie J, Capecchi B, Serruto D, Rappuoli R, Pizza M

IRIS, Chiron SpA, Via Fiorentina 1, 53100, Siena, Italy

[Medline record in process]
 

During the last century, several approaches have been used for the development of vaccines, going from the immunization with live-attenuated bacteria up to the formulation of the safer subunit vaccines. This conventional approach to vaccine development requires cultivation of the pathogen and its dissection using biochemical, immunological and microbiological methods. Although successful in several cases, this method is time-consuming and failed to provide a solution for many human pathogens. Now genomic approaches allow for the design of vaccines starting from the prediction of all antigens in silico, independently of their abundance and without the need to grow the microorganism in vitro. A new strategy, termed "Reverse Vaccinology", which has been successfully applied in the last few years, has revolutionized the approach to vaccine research. The Neisseria meningitidis serogroup B project, the first example of Reverse Vaccinology, as well as the application of this strategy to develop novel vaccines against other human pathogens are discussed.

PMID: 12531326, UI: 22420253

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Vaccine 2003 Jan 30;21(7-8):601-4
 

Recent progress in the development of vaccines for infants and children.

McIntosh ED, Paradiso PR

Wyeth, Huntercombe Lane South, Taplow, Berkshire SL6 0PH, Maidenhead, UK

[Medline record in process]
 

Infectious agents do not respect national or international boundaries. Attempts to prevent their spread, and the diseases which they cause, involve implementing vaccination as widely and as appropriately as possible. The principles of vaccination against infectious agents are now being applied to cancer and other non-infectious conditions. In order to understand where modern vaccinology is heading, it is necessary to first examine individual components. This brief overview examines the following: Streptococcus pneumoniae, Neisseria meningitidis, varicella zoster, measles, rotavirus, HIV, influenza, "emerging" viral infections and cancer.

PMID: 12531325, UI: 22420252

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Vaccine 2003 Jan 30;21(7-8):596-600
 

The global value of vaccination.

Ehreth J

Department of Health Systems Management, Tulane University, Medtronic Europe SA, Route du Molliau 31, CH-1131, Tolochenaz, Switzerland

[Medline record in process]
 

While most agree that vaccination is one of the most important public health practices, vaccines continue to be underused and undervalued, and vaccine-preventable diseases remain a threat to world health. Perhaps one reason this gap remains is that decision-making generally is made on a vaccine-by-vaccine basis. There has been less attention to the value of vaccination in general. To more clearly identify this value, this paper reviews the cost-effectiveness literature and calculates the annual benefits of vaccination on a global scale.

PMID: 12531324, UI: 22420251

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Vaccine 2003 Jan 30;21(7-8):593-5
 

Vaccinology: past achievements, present roadblocks and future promises.

Andre FE

GlaxoSmithKline Biologicals, Rixensart, Belgium

[Medline record in process]
 

Of all the branches of modern medicine, vaccinology can claim to be the one that has contributed most to the relief of human misery and the spectacular increase in life expectancy in the last two centuries. It is the only science that has eradicated an infectious disease-smallpox-responsible for 8-20% of all deaths in several European countries in the 18th century. Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication. Currently, it is estimated that immunization saves the lives of 3 million children a year but 2 million more lives could be saved by existing vaccines. The success of vaccines in controlling and eliminating diseases has, paradoxically, been the cause of a revival of the anti-vaccination movement which in the absence, in developed countries, of many erstwhile common infectious diseases such as diphtheria, tetanus, polio, pertussis, measles, rubella and mumps has come to believe that vaccination is not only no longer necessary but is even dangerous. This is because it accepts, as "reactions", any untoward health event that occurs after administration of a vaccine. Most vaccine "reactions", therefore, appear to be more frequent than vaccine-preventable diseases. Public Health Authorities, aware of the great value of vaccines to society, are facing an uphill battle to get them accepted by a growing proportion of so-called educated minorities, thus endangering disease elimination. Other developments, in the last two decades, that have hampered vaccine usage have been the exploding costs of research, development and manufacture of new vaccines and the emphasis still placed on therapy in preference to prevention in medicine. This has led to the erroneous perception that vaccines are expensive although they are, in most cases, more cost-effective than the popular wait-see-treat approach. A favorable trend for vaccinology has been fuelled by recent major breakthroughs in the sciences of immunology, molecular biology, genomics, proteomics, physico-chemistry and computers that promise a bright future for prevention, not only of acute infectious diseases, but also treatment of conditions like chronic infections, allergy, auto-immune diseases and cancer where some malfunctioning of the immune system is thought to play a part. Vaccines are being made more user-friendly by the development of combined vaccines and less painful and invasive inoculation techniques than the traditional syringe and needle. Recent new initiatives, like the Global Alliance on Vaccines and Immunization (GAVI),which are gathering new sources of funding for vaccination, should be beneficial for vaccinology.

PMID: 12531323, UI: 22420250

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Vaccine 2003 Jan 30;21(7-8):587-92
 

New tendencies and strategies in international immunisation: GAVI and The Vaccine Fund.

Martin JF, Marshall J

The Vaccine Fund, Fonds Mondial pour les Vaccins, 36 Quai Fulchiron, 69005, Lyon, France

[Medline record in process]
 

It is now accepted that investment in health is an important contributor to poverty reduction; however failure to immunise the world's children with readily available life-saving vaccines results in more than 3 million premature deaths annually.The Vaccine Fund-a new structural tool with a clear mission "every child every where" and the Global Alliance for Vaccines and Immunization (GAVI)-a true alliance of all global stakeholders, are working together to build sustainability of immunisation and immunisation capacity in the world's poorest countries.Substantial funding for immunisation has been raised but more is needed to complete the task of fully immunising the world's poorest children.

PMID: 12531322, UI: 22420249

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Vaccine 2003 Jan 30;21(7-8):580-1
 

Towards the new global vaccinology era in prevention and control of diseases.

Kurstak PD

Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Infections Control World Organization, Que., H3C 3J7, Montreal, Canada

[Medline record in process]
 

PMID: 12531320, UI: 22420247

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