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Indian Pediatr 2003 Jan;40(1):75-6
 

Hib Vaccination controversy and the Declaration of Commercial Interest.

Taneja V

Department of Pediatrics, Sir Ganga Ram Hospital, New Delhi - 110 060.

[Medline record in process]
 

PMID: 12554930, UI: 22442064

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J Infect Dis 2003 Jan 15;187(2):226-42
 

Moving to human immunodeficiency virus type 1 vaccine efficacy trials: defining T cell responses as potential correlates of immunity.

Russell ND, Hudgens MG, Ha R, Havenar-Daughton C, McElrath MJ

Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, and Department of Medicine, University of Washington, Seattle, Washington, USA.

[Medline record in process]
 

There is evidence in both simian immunodeficiency virus and human immunodeficiency virus (HIV) type 1 infection that class I major histocompatibility complex-restricted CD8(+) cytotoxic T lymphocytes play a pivotal role in controlling infection and, potentially, in protecting by immunization. Progress has been made in designing strategies to elicit these responses with HIV-1 vaccines, but methods to reproducibly quantify them have posed difficulties. An interferon-gamma enzyme-linked immunospot assay, using peptide pools spanning the HIV-1 genes, was developed and standardized. This method is rapid (2 days), sensitive (threshold of detection, >/=0.005%), quantitative, feasible using cryopreserved cells, and able to define epitope specificities. When this assay was applied to 36 HIV-1-seropositive and 10 HIV-1-seronegative subjects, it proved to be robust (specificity, 100%). When responses in natural infection were compared with vaccine-induced responses, vaccine recipient responses were >/=1 log lower, which confirms the importance of using this sensitive assay as an initial screen in vaccine protocols.

PMID: 12552447, UI: 22439927

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J Infect Dis 2003 Feb 1;187(3):513-7
 

Lipoarabinomannan-reactive human secretory immunoglobulin a responses induced by mucosal bacille calmette-guerin vaccination.

Brown RM, Cruz O, Brennan M, Gennaro ML, Schlesinger L, Skeiky YA, Hoft DF

Saint Louis University Vaccine and Treatment Evaluation Unit, Division of Infectious Diseases and Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.

[Medline record in process]
 

The ability of 17 recombinant mycobacterial proteins, native antigen 85 complex, lipoarabinomannan (LAM), and Mycobacterium tuberculosis lysate to detect antibody responses induced by bacille Calmette-Guerin (BCG) vaccination and active tuberculosis infection were studied in enzyme-linked immunosorbent assays. Only LAM-reactive serum immunoglobulin G responses were significantly increased in both BCG-vaccinated patients and patients with active tuberculosis (P<.05), and oral BCG vaccination also induced significant increases in LAM-reactive secretory immunoglobulin A (P<.05). LAM-reactive antibody assays can serve as markers of humoral and mucosal immunity in future trials of BCG and newer attenuated mycobacterial vaccines.

PMID: 12552438, UI: 22439969

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J Infect Dis 2003 Feb 1;187(3):495-9
 

Does antigen-specific cytokine response correlate with the experience of oculorespiratory syndrome after influenza vaccine?

Skowronski DM, Lu H, Warrington R, Hegele RG, De Serres G, HayGlass K, Stark D, White R, Macnabb J, Li Y, Manson HE, Brunham RC

University of British Columbia Centre for Disease Control, Epidemiology Services, Vancouver, British Columbia, Canada. danuta.skowronski@bccdc.ca

[Medline record in process]
 

During the 2000-2001 season in Canada, a newly identified oculorespiratory syndrome (ORS) was observed in patients after immunization with inactivated influenza vaccine. ORS was associated with a high proportion of microaggregates of unsplit virions in the implicated vaccine and had clinical features suggesting delayed-onset hypersensitivity. We explore the association between in vitro cytokine balance (type 1 vs. type 2) and clinical ORS after influenza vaccination. We report the balance of interferon (IFN)-gamma, interleukin (IL)-10, IL-5, and IL-13 expression by peripheral blood mononuclear cells (PBMC) among unvaccinated, vaccinated ORS-affected, and vaccinated ORS-unaffected persons after in vitro challenge with implicated and nonimplicated vaccines. Antigen-stimulated PBMC from vaccinated persons produced significantly more IFN-gamma than did those from unvaccinated persons. There was a statistically significant type 2 polarization among unvaccinated compared with vaccinated persons. Although vaccinated ORS-affected individuals had less of a type 1 basis than did vaccinated unaffected individuals, this difference was not statistically significant.

PMID: 12552434, UI: 22439965

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J Infect Dis 2003 Jan 1;187(1):117-23
 

Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette-Guerin attenuation.

Lewis KN, Liao R, Guinn KM, Hickey MJ, Smith S, Behr MA, Sherman DR

Department of Pediatrics, University of Washington, Seattle 98195, USA.

The tuberculosis (TB) vaccine bacille Calmette-Guerin (BCG) is a live attenuated organism, but the mutation responsible for its attenuation has never been defined. Recent genetic studies identified a single DNA region of difference, RD1, which is absent in all BCG strains and present in all Mycobacterium tuberculosis (MTB) strains. The 9 open-reading frames predicted within this 9.5-kb region are of unknown function, although they include the TB-specific immunodominant antigens ESAT-6 and CFP-10. In this study, RD1 was deleted from MTB strain H37Rv, and virulence of H37Rv:DeltaRD1 was assessed after infections of the human macrophage-like cell line THP-1, human peripheral blood monocyte-derived macrophages, and C57BL/6 mice. In each of these systems, the H37Rv:DeltaRD1 strain was strikingly less virulent than MTB and was very similar to BCG controls. Therefore, it was concluded that genes within or controlled by RD1 are essential for MTB virulence and that loss of RD1 was important in BCG attenuation.

PMID: 12508154, UI: 22396205

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J Infect Dis 2003 Jan 1;187(1):109-16
 

Prevention of Haemophilus influenzae type b (Hib) meningitis and emergence of serotype replacement with type a strains after introduction of Hib immunization in Brazil.

Ribeiro GS, Reis JN, Cordeiro SM, Lima JB, Gouveia EL, Petersen M, Salgado K, Silva HR, Zanella RC, Almeida SC, Brandileone MC, Reis MG, Ko AI

Goncalo Moniz Research Center, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Bahia, Brazil.

Surveillance for Haemophilus influenzae meningitis cases was performed in Salvador, Brazil, before and after introduction of H. influenzae type b (Hib) immunization. The incidence of Hib meningitis decreased 69% during the 1-year period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000 person-years; P<.001). In contrast, the incidence for H. influenzae type a meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years; P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H. influenzae type a isolates belonged to 2 clonally related groups, both of which were found before Hib immunization commenced. Therefore, Hib immunization contributed to an increased risk for H. influenzae type a meningitis through selection of circulating H. influenzae type a clones. The risk attributable to serotype replacement is small in comparison to the large reduction in Hib meningitis due to immunization. However, these findings highlight the need to maintain surveillance as the use of conjugate vaccines expands worldwide.

PMID: 12508153, UI: 22396204

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J Virol 2003 Feb 15;77(4):2587-2599
 

Molecular Characteristics of Human Immunodeficiency Virus Type 1 Subtype C Viruses from KwaZulu-Natal, South Africa: Implications for Vaccine and Antiretroviral Control Strategies.

Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse Van Rensburg E, Mosam A, Smith A, Cassol S

HIV-1 Molecular Virology and Bioinformatics Laboratories, Africa Centre for Health and Population Studies and the Nelson R. Mandela School of Medicine. Centre for HIV/AIDS Networking. Department of Dermatology. Department of Virology, University of Natal. Medical Research Council, Durban. Department of Medical Virology, University of Stellenbosch and Tygerberg Hospital, Tygerberg, South Africa. Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.

[Record supplied by publisher]
 

The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naive patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.

PMID: 12551997

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J Virol 2003 Feb 15;77(4):2522-2529
 

Effective Vaccination against Long-Term Gammaherpesvirus Latency.

Tibbetts SA, McClellan JS, Gangappa S, Speck SH, Virgin HW 4th

Department of Pathology & Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110. Department of Microbiology & Immunology, Yerkes Regional Primate Center, Emory University, Atlanta, Georgia 30329.

[Record supplied by publisher]
 

The fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. Recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achieving sterilizing immunity against gammaherpesviruses. Using the murine gammaherpesvirus 68 (gammaHV68) system, we demonstrate that it is possible to effectively vaccinate against long-term latency. By immunizing mice with a gammaHV68 mutant virus that is deficient in its ability to reactivate from latency, we reduced latent infection of wild-type challenge virus to a level below the limit of detection. Establishment of latency was inhibited by vaccination regardless of whether mice were challenged intraperitoneally or intranasally. Passive transfer of antibody from vaccinated mice could partially reconstitute the effect, demonstrating that antibody is an important component of vaccination. These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal.

PMID: 12551990

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Lancet 2003 Jan 11;361(9352):148
 

Polio resurgence in Indian state causes concern.

Sharma DC

Publication Types:
 

• News

PMID: 12531589, UI: 22419845

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MMWR Morb Mortal Wkly Rep 2003 Jan 10;52(1):4-6
 

Accelerated measles control--Cambodia, 1999-2002.

Cambodia is recovering from approximately 30 years of civil war that resulted in the breakdown of the country's public health infrastructure. In 1999, the Ministry of Health initiated a measles-control program with the goal of reducing the annual incidence of measles to <10,000 cases in 2005 by strengthening measles surveillance, improving routine vaccination coverage, implementing supplementary measles immunization activities (SIAs), and providing vitamin A during outbreak investigations and SIAs. This report summarizes measles-vaccination activities and their impact in reducing reported measles cases from 13,827 in 1999 to 1,234 in 2002 and suggests options for future measles-control efforts in postconflict situations.

PMID: 12549899, UI: 22436994

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N Engl J Med 2003 Jan 30;348(5):414
 

Images in clinical medicine. Progression of the lesion at the site of inoculation after smallpox vaccination.

Rubins K, Relman DA

Stanford University School of Medicine, Stanford, CA 94305, USA.

[Medline record in process]
 

PMID: 12556544, UI: 22444737

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Pediatr Infect Dis J 2002 Dec;21(12):1180-1
 

Recommendations for parents adopting an infant with chronic hepatitis B.

Skurkovich B

Brown Medical School, Providence, RI, USA.

PMID: 12488671, UI: 22376862

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Pediatr Infect Dis J 2002 Jul;21(7):685-96
 

Current concepts on active immunization against respiratory syncytial virus for infants and young children.

Kneyber MC, Kimpen JL

Wilhelmina Children's Hospital/University Medical Center, Utrecht, The Netherlands.

Respiratory syncytial virus (RSV) is the most important causative agent of viral respiratory tract infections in infants and young children. Passive immunization against RSV became available recently, but this does not apply to an effective vaccine as a result of dramatic adverse results of immunization with a RSV candidate vaccine in the 1960s and the lack of full knowledge of the immune response induced by RSV. Nonetheless intensive research during the past two decades has resulted in several interesting candidate vaccines, of which some have gone through testing in humans. These include the subunit vaccines PFP-1, PFP-2, BBG2Na and cold-passaged/temperature-sensitive mutants. The development of candidate vaccines against RSV is discussed. Because of questions, uncertainties and difficulties with the development of effective vaccines against RSV, it will probably be at least another 5 to 10 years before routine immunization against RSV becomes available.

Publication Types:
 

• Review
• Review, tutorial

PMID: 12237605, UI: 22225069

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Science 2003 Jan 10;299(5604):181
 

Bioterrorism. New look at old data irks smallpox-eradication experts.

Enserink M

Publication Types:
 

• News

PMID: 12522221, UI: 22410702

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Vaccine 2003 Mar 7;21(11-12):1292-9
 

Vaccination with DNA encoding ORFF antigen confers protective immunity in mice infected with Leishmania donovani.

Sukumaran B, Tewary P, Saxena S, Madhubala R

School of Life Sciences, Jawaharlal Nehru University, 110067, New Delhi, India

[Medline record in process]
 

The gene ORFF is part of the multigenic LD1 locus on chromosome 35 that is frequently amplified in Leishmania. The function of ORFF is unknown. The gene encoding ORFF was cloned into a eukaryotic expression vector downstream to the cytomegalovirus (CMV) promoter. BALB/c mice were injected intramuscularly with ORFF DNA and challenged with Leishmania donovani promastigotes. Vaccination with ORFF gene induced both humoral and cellular immune response against ORFF, which provided significant level of protection against challenge with L. donovani. A qualitative PCR was used to determine whether activation of Th1 cells develops selectively in response to this ORFF DNA vaccine. The results indicated that mRNA for IFN-gamma was significantly induced in immunized mice. No significant change in IL-4 mRNA expression was observed in mice immunized with ORFF DNA vaccine versus mice immunized with control plasmid. Thus, DNA immunization may offer an attractive alternative strategy against leishmaniasis.

PMID: 12559811, UI: 22448556

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Vaccine 2003 Mar 7;21(11-12):1282-1291
 

Construction and characterisation of O139 cholera vaccine candidates.

Ledon T, Valle E, Valmaseda T, Cedre B, Campos J, Rodri;guez BL, Marrero K, Garci;a H, Garci;a L, Fando R

Grupo de Genetica, Centro Nacional de Investigaciones Cienti;ficas, AP 6412, Havana, Cuba

[Record supplied by publisher]
 

The hemagglutinin/protease (HA/P) seems to be an attractive locus for the insertion of heterologous tags in live cholera vaccine strains. A DeltaCTXPhi spontaneous mutant derived from a pathogenic strain of O139 Vibrio cholerae was sequentially manipulated to obtain hapA Colon, two colons celA derivatives which were later improved in their environmental safety by means of a thyA mutation. All the strains here obtained showed similar phenotypes in traits known to be remarkable for live cholera vaccines irrespective of their motility phenotypes, although the hapA mutants had a 10-fold decrease in their colonisation capacity compared with their parental strains in the infant mouse cholera model. However, the subsequent thyA mutation did not affect their colonisation properties in the same model. These preliminary results pave the way for further clinical assays to confirm the possibilities of these vaccine prototypes as safe and effective tools for the prevention of O139 cholera.

PMID: 12559810

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Vaccine 2003 Mar 7;21(11-12):1268-74
 

Comparison of the reactogenicity and immunogenicity of a split and a subunit-adjuvanted influenza vaccine in elderly subjects.

Squarcione S, Sgricia S, Biasio LR, Perinetti E

Direzione Sanitaria-Azienda IRCCS, Ospedale Lazzaro Spallanzani, Via Portuense, 292, 00149, Rome, Italy

[Medline record in process]
 

A randomised, open study was carried out among an elderly population in order to compare the reactogenicity and immunogenicity of an inactivated, split virion influenza vaccine (Vaxigrip((R)), Aventis Pasteur MSD, Lyon, France) with that of an MF59-adjuvanted, subunit vaccine (Fluad((R)), Chiron Vaccines, Siena, Italy). Both vaccines contained the three strains: A/Sydney/5/97 (H3N2), A/Beijing/262/95 (H1N1) and B/Beijing/184/93, recommended by the WHO for the 1998-1999 influenza season. A total of 2150 subjects were vaccinated and included in the reactogenicity analysis. A total of 1076 subjects received Vaxigrip((R)) (age 73.3+/-5.9 years, 49.6% men) and 1074 subjects received Fluad((R))(age 73.4+/-5.9 years, 52.3% men). All subjects were kept under medical observation for 30min after vaccination, in order to check any immediate local and/or systemic reaction. A self monitoring diary card was given to all subjects to collect any local and/or systemic reaction occurring during the 3 days following the vaccination, any adverse event occurring between vaccination day and 21st day post-vaccination and any medication taken during the study period.A total of 1186 subjects were included in the immunogenicity analysis. A total of 591 subjects received Vaxigrip((R)) (age 73.4+/-5.6 years, 52.3% men) and 595 subjects received Fluad((R)) (age 73.8+/-5.9 years, 55.8% men). Blood samples were collected pre- and 21 days post-vaccination and were analysed by the haemagglutination inhibition assay.In terms of reactogenicity both vaccines were generally well tolerated. The frequency of local reactions was lower in the group that received Vaxigrip((R)). Pain at the injection site occurring from 30min to 3 days after vaccination was also significantly less frequent (P=0.005) in the Vaxigrip((R)) group. Fever >/=37.5 degrees C was reported in less than 1% of all vaccinated subjects. No serious adverse event was related to vaccine administration.In terms of immunogenicity both vaccines induced an effective immune response (anti-HI titre >/=40) against A/Sydney/5/97 (H3N2) and A/Beijing/262/95 (H1N1) strains in the entire population. Vaxigrip((R)) and Fluad((R)) induced similar seroprotection and seroconversion rates against the A/Sydney/5/97 (H3N2) strain. For both vaccines a lower percentage of subjects achieved a seroprotective titre >/=40 against the B/Beijing/184/93. A lower antibody response against the influenza B strain was also observed in other studies conducted during the same season. In subjects 75 years of age or older, Fluad((R)) was more immunogenic than Vaxigrip((R)) for all three virus strains.

PMID: 12559808, UI: 22448553

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Vaccine 2003 Mar 7;21(11-12):1256-67
 

The cost-effectiveness of routine childhood varicella vaccination in Germany.

Banz K, Wagenpfeil S, Neiss A, Goertz A, Staginnus U, Vollmar J, Wutzler P

Outcomes International, Malzgasse 9, CH-4052, Basel, Switzerland

[Medline record in process]
 

This study explores the economic value of a routine varicella vaccination program for Germany. An age-structured decision analytic model was used to assess the benefits, costs and cost-effectiveness of an immunization program for a period of 30 years. Three interventions were compared with no vaccination: universal vaccination of around 15 months old healthy children, vaccination of susceptible adolescents (11-12 years of age), and the combined strategy. The analysis was conducted from both the societal perspective and the payers', i.e. sickness funds, perspective. Input data were mainly derived from a retrospective survey (analyzed were1334 patient records) and from a seroprevalence study (n=4602 sera). Using a coverage rate of 85% and a vaccine efficacy rate of 86% routine children vaccination could prevent around 611,000 varicella cases and over 4700 major complications per year. Average yearly cost savings for the society are 51.3 million Euro. The benefit-cost ratio (BCR) is 4.12. From the third-party payer's perspective, the BCR is 1.75 which is a consequence of significant reimbursement of parent's lost earnings by German sickness funds. The adolescent vaccination strategy has a favorable BCR ratio of 8.44 from the societal perspective, but clearly inferior medical effects. The combined vaccination strategy showed similar results as the children strategy. Routine childhood varicella vaccination appears to be a highly efficient strategy to reduce the burden of varicella and results in significant savings for both the society and the payers.

PMID: 12559807, UI: 22448552

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Vaccine 2003 Mar 7;21(11-12):1232-8
 

Recombinant raccoon pox vaccine protects mice against lethal plague.

Osorio JE, Powell TD, Frank RS, Moss K, Haanes EJ, Smith SR, Rocke TE, Stinchcomb DT

Heska Corporation, 1613 Prospect Parkway, 80525, Ft. Collins, CO, USA

[Medline record in process]
 

Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7x10(4)LD(50)). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IRES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague.

PMID: 12559803, UI: 22448548

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Vaccine 2003 Mar 7;21(11-12):1224-31
 

Safety and immunogenicity of a live-attenuated influenza vaccine blended and filled at two manufacturing facilities.

Nolan T, Lee MS, Cordova JM, Cho I, Walker RE, August MJ, Larson S, Coelingh KL, Mendelman PM

Clinical Epidemiology and Biostatistics Unit, Department of Paediatrics, University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital, Vict., Melbourne, Australia

[Medline record in process]
 

This study was designed to compare the safety and immunogenicity of a trivalent live-attenuated, cold-adapted influenza vaccine (CAIV-T) blended and filled at two different manufacturing facilities (Medeva and Aviron-PA). The vaccines contained approximately 10(7) TCID(50) (median tissue culture infectious dose) of each of the three recommended 1997-1998 influenza vaccine components, A/Shenzhen/227/95 (H1N1) (A/Bayern/7/95 (H1N1)-like strain), A/Wuhan/359/95 (H3N2), and B/Ann Arbor/1/94 (B/Beijing/184/93-like strain). Two hundred and twenty-five healthy Australian children aged 12-42 months were enrolled and randomized in a 3:2 ratio to receive CAIV-T blended and filled either at Medeva or at Aviron-PA. Two doses of CAIV-T were given 4-6 weeks apart as an intranasal spray. Three blood specimens were collected (immediately before doses one and two, and 28+/-5 days following dose two) for measuring hemagglutination inhibition (HAI) antibody responses. Adverse events occurring within 10 days and serious adverse events occurring within 42 days were collected. Serum HAI antibody levels were measured against the three vaccine strains. Equivalent immunogenicity between the two vaccine groups was pre-specified as: (1) within 20% difference in seroconversion rates (HAI titers >/=4-fold rise); and (2) within 4-fold difference in the 90% confidence interval of geometric mean titer ratio. Among 10 pre-specified adverse events, only vomiting had significantly different incidence rates in the two vaccine groups following dose one (3% versus 13%, P=0.01) but the difference disappeared following dose two (4% versus 4%). Differences in seroconversion rates following dose two between the two vaccine groups in pre-vaccination seronegative children were all <20% for the three vaccine strains (16% for H1N1, 0% for H3N2, and 0% for B). The results indicate that CAIV-T blended and filled in the two facilities had equivalent profiles of safety and immunogenicity.

PMID: 12559802, UI: 22448547

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Vaccine 2003 Mar 7;21(11-12):1180-1186
 

Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine.

Muszkat M, Greenbaum E, Ben-Yehuda A, Oster M, Yeu'l E, Heimann S, Levy R, Friedman G, Zakay-Rones Z

Geriatric Unit, Department of Medicine, Hadassah University Hospital, Jerusalem, Israel

[Record supplied by publisher]
 

Intramuscular (IM) influenza vaccines are only 30-40% effective in preventing clinical illness among the elderly, and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among nursing-home elderly.Twenty-one institutionalized elderly subjects were vaccinated IN with an inactivated novel vaccine, twice, 21 days apart, and with no adverse effects. Twenty-two subjects were vaccinated once with a commercial IM vaccine. Viral strains used in the 1998/9 vaccine (20&mgr;g of each per dose) were A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94. Serum antibodies (IgG and IgM) and nasal IgA were determined by the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA), respectively.Mucosal antibody response to the three vaccine strains was detected in 47.6-71.4% and 18.1-31.8% of IN and IM immunized subjects, respectively. Serum antibody response to the three antigens tested was detected in 20.0-61.9% and 18.2-72.7% of IN and IM immunized subjects, respectively. Seroconversion was not significantly different after IN or IM vaccination for both A/Sydney and B/Harbin, but higher for A/Beijing following IM vaccination. On study completion, 57.1, 65.0 and 50.0% of IN vaccinees were seroprotected to A/Beijing, A/Sydney and B/Harbin, respectively. Similarly, 68.1, 77.2 and 54.5% were immune after IM vaccination.The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of morbidity and complications in nursing-home elderly.

PMID: 12559796

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Vaccine 2003 Mar 7;21(11-12):1174-9
 

Revaccination of healthy nonresponders with hepatitis B vaccine and prediction of seroprotection response.

Kim MJ, Nafziger AN, Harro CD, Keyserling HL, Ramsey KM, Drusano GL, Bertino JS

Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, 13326-1394, Cooperstown, NY, USA

[Medline record in process]
 

Sixty healthy nonresponders were randomized to receive intramuscular (IM) high dose hepatitis B virus (HBV) vaccine versus IM standard dose HBV vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) at 0-2 months. Antibody to hepatitis B surface antigen was measured 1 month after each dose and 3 months after the last dose. Two regimens were equivalent in eliciting seroprotection in nonresponders. Weight-height index (WHI) <39 and alanine transaminase (ALT) <39mg/dl predicted which nonresponders would seroconvert. A three-dose regimen of standard dose HBV vaccine plus GM-CSF may be a useful for seroprotection of healthy nonresponders.

PMID: 12559795, UI: 22448540

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Vaccine 2003 Mar 7;21(11-12):1165-1173
 

Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant.

Isaka M, Yasuda Y, Taniguchi T, Kozuka S, Matano K, Maeyama J, Morokuma K, Ohkuma K, Goto N, Tochikubo K

Department of Microbiology, Nagoya City University Medical School, Mizuho-ku, 467-8601, Nagoya, Japan

[Record supplied by publisher]
 

To investigate the possibility of intranasal immunization with an acellular pertussis vaccine, groups of mice were administered intranasally with aluminium-non-adsorbed pertussis toxoid (PTd; 0.5 or 5&mgr;g) and formalin-treated filamentous hemagglutinin (fFHA; 5&mgr;g) with and without recombinant cholera toxin B subunit (rCTB; 10&mgr;g) as a mucosal adjuvant. At a low concentration of PTd, the following things became clear: (1) earlier and higher elevation of serum anti-PTd and anti-FHA IgG antibody titres in the presence of rCTB than in its absence, (2) higher serum anti-PTd and anti-FHA IgG antibody titres than 200 and 100ELISA unitsml(-1) (EUml(-1)) in all mice, respectively, in the presence of rCTB, which were obtained by calibration against a reference anti-pertussis mouse serum, and (3) in an intranasal challenge experiment with Bordetella pertussis, slightly more rapid elimination of the bacteria from the lungs of mice intranasally immunized in the presence of rCTB, suggesting the effectiveness of rCTB as a mucosal adjuvant. However, irrespective of rCTB and dose of PTd, mice which were immunized four times and sacrificed on day 35 developed high levels of anti-PTd serum IgG antibodies, high or moderate levels of anti-FHA serum IgG antibodies and mucosal anti-PTd IgA antibodies in the lungs; only a slight or no increase of anti-FHA mucosal IgA antibodies was observed in the lung. These facts suggested the immunogenicity and mucosal adjuvanticity of PTd, and therefore, the mucosal adjuvanticity of rCTB seemed to be inconspicuous. Moreover, the addition of rCTB induced higher anti-PTd serum IgE antibody responses than no addition of it depending on dose of PTd. These results show that dose of PTd included in an acellular pertussis vaccine had better be low as possible and the addition of rCTB may not be always necessary in case of this nasal vaccine alone unlike tetanus and diphtheria toxoids and hepatitis B virus vaccine reported before.

PMID: 12559794

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Vaccine 2003 Mar 7;21(11-12):1158-64
 

Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production.

Woolums AR, Siger L, Johnson S, Gallo G, Conlon J

Department of Large Animal Medicine, College of Veterinary Medicine, 30602, Athens, GA, USA

[Medline record in process]
 

The objective of this study was to determine the effect of vaccination with commercially-available multivalent vaccines containing either modified-live (MLV) bovine herpesvirus-1 (BHV-1) (Bovishield((R))) or MLV plus killed (MLV+K) BHV-1 (Reliant((R)) Plus) on protection against challenge at 5 days after a single vaccination. An additional objective was to determine whether cell-mediated immunity as measured by virus-specific interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) was associated with any early protection induced by vaccination. Clinical signs, serum neutralizing (SN) titers, and nasal virus isolation (VI) titers were also measured. The 12-16-week-old dairy cross-calves seronegative for antibodies to BHV-1 were vaccinated with a multivalent vaccine containing MLV BHV-1 (n=19), a multivalent vaccine containing MLV+K BHV-1 (n=19), or a control multivalent vaccine not containing BHV-1 (n=10) on day 0 and challenged intranasally on day 5. PBMC were isolated on days 0, 3, 5, 8, 10, 14 and 19. PBMC were incubated in vitro with spent media, live BHV-1, or heat-inactivated BHV-1 for 72h. Supernatants were assayed for bovine IFN-gamma by ELISA. Bovine herpesvirus-1-specific IFN-gamma production was expressed as percent of the kit positive control, with value for spent media subtracted. Clinical signs were monitored daily. Serum VN titers were measured on days 0-5 and 19. Nasal VI titer was measured every other day from days 5 to 19. Interferon gamma production was higher on day 5, and was significantly increased post-challenge, in both vaccine groups compared to controls. There was no difference between vaccine groups on any day. There was no significant difference in SN titer among groups on any day. Virus isolation titer was significantly higher in controls on days 6 and 8 compared to both vaccine groups. Temperatures were significantly higher and nasal discharge was present more often post-challenge in controls compared to vaccine groups. Vaccination 5 days prior to challenge with commercially-available vaccine containing MLV or MLV+K BHV-1 was associated with increased BHV-1-specific IFN-gamma production, decreased viral shedding, lower temperatures and less nasal discharge post-challenge. Cell mediated immune responses as measured by IFN-gamma production are stimulated rapidly following BHV-1 vaccination of calves.

PMID: 12559793, UI: 22448538

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Vaccine 2003 Mar 7;21(11-12):1149-1157
 

Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants.

Rivera E, Hu S, Concha C

National Veterinary Institute, S-751 89, Uppsala, Sweden

[Record supplied by publisher]
 

The dry extract prepared from the Panax ginseng C.A. Meyer-root (total ginseng (T-ginseng)) contain ginsenosides (G-des) which were shown to have adjuvant properties as demonstrated by:injecting guinea pigs with a mixture of T-ginseng and inactivated porcine parvovirus (PPV) as a conventional vaccine;injecting PPV-antigen and T-ginseng simultaneously but separately at different sites on the animal andinjecting only the T-ginseng 1 or 2 weeks prior to immunisation with the PPV-antigen.Using a haemagglutination inhibition (HI) test in the antibody titration, it was found that the mean HI-titre for the animals injected with PPV-antigen only was 320+/-0. By comparison, the mean titre value was 2026+/-1206 for the sera from the animals injected with the same vaccine but adjuvanted with 4mg of T-ginseng, while the antibody titre induced by a vaccine containing Al(OH)(3)-gel was 2986+/-1596. Interestingly, the T-ginseng and Al(OH)(3) acted synergistically and further improved the antibody response to the PPV-antigen to 6826+/-2413, i.e. more than 20 times the HI titre of the non-adjuvanted PPV-vaccine. Immunisations using PPV-vaccines adjuvanted with single purified G-des demonstrated that the ginseng fractions Rb1 and Rg1 are potent adjuvants inducing higher or similar antibody titres than the vaccine adjuvanted with Al(OH)(3), e.g. Rb1 tested at a concentration of 830&mgr;g per dose induced a significantly (P=0.009) higher antibody titre than the one adjuvanted with Al(OH)(3). Nevertheless, different than the mixture Al(OH)(3)-T-ginseng; Rb1 and Rg1 act antagonistically and partially inhibit each other. The G-des adjuvanted vaccines induced significantly (P=0.0011) higher titres of IgG2 antibodies compared with IgG1.

PMID: 12559792

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Vaccine 2003 Mar 7;21(11-12):1137-48
 

Influenza vaccine uptake in the elderly: results from a rapid assessment of the effectiveness of new government policy in England for the winters 2000/2001 and 2001/2002.

Joseph C, Goddard N

PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, NW9 5EQ, London, UK

[Medline record in process]
 

Immunisation against influenza is an important means of reducing morbidity and mortality amongst high-risk groups, and especially the elderly. Although immunisation has been recommended for these groups for many years, no timely or comprehensive monitoring at the national level was carried out in England before the beginning of this century. Annual numbers of doses administered were available, but not to whom they were given. This paper describes the results of a national rapid reporting scheme for England that was introduced by the Department of Health (DH) and PHLS Communicable Disease Surveillance Centre (CDSC). The scheme collected monthly data on influenza immunisation uptake among people aged 65 or more during the winters of 2000/2001 and 2001/2002. Results showed that DH annual targets of 60 and 65%, respectively were both met, although considerable variation occurred at the local levels. The feasibility of this method of monitoring immunisation uptake in the elderly is discussed.

PMID: 12559791, UI: 22448536

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Vaccine 2003 Mar 7;21(11-12):1118-24
 

Total genome polymorphism and low frequency of intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis in otitis prone and non-prone children up to 2 years of age. Consequences for vaccine design?

Hays JP, van der Schee C, Loogman A, Eadie K, Verduin C, Faden H, Verbrugh H, van Belkum A

Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam (EMCR), Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

[Medline record in process]
 

Intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis was studied using pulsed field gel electrophoresis (PFGE) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. From a set of 91 M. catarrhalis isolates, 19 pairs of PFGE identical isolates were found. Five pairs originated from otitis non-prone children, 11 pairs from otitis prone children and for 3 pairs, one of the pair originated from an otitis prone and the other from an otitis non-prone child. No particular M. catarrhalis isolate was associated with either the otitis prone or non-prone children. One of these 19 pairs of isolates was found to exhibit both uspA1 and uspA2 intra-genomic variation, whilst another pair exhibited uspA2 intra-genomic variation only. Sequence data obtained from these variants showed that PCR-RFLP pattern differences reflected actual changes in predicted amino acid composition and that minor amino acid changes in a 23 base pair "NINNIY" repeat region (a conserved UspA1 and UspA2 binding site for the neutralising antibody mAb17C7) occurred. Variation in the uspA2 5' non-coding "AGAT" repeat region was also observed. These results may have implications for future M. catarrhalis vaccines comprising UspA1 or UspA2 components.

PMID: 12559789, UI: 22448534

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Vaccine 2003 Mar 7;21(11-12):1112-7
 

Construction of designer glycoconjugate vaccines with size-specific oligosaccharide antigens and site-controlled coupling.

Wang JY, Chang AH, Guttormsen HK, Rosas AL, Kasper DL

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, 02115, Boston, MA, USA

[Medline record in process]
 

Coupling of carbohydrate antigens to protein carriers is a typical approach to enhancing the immunogenicity of carbohydrate-based vaccines. Glycoconjugates with well-defined structures are needed for studies defining the structural variables that govern antibody responses. We report a chemical strategy for preparation of an array of glycoconjugates containing saccharides of desired molecular sizes by selective depolymerization of bacterial polysaccharides and chemically controlled site-specific coupling. As an example, we synthesized and evaluated an oligosaccharide-based vaccine against type III group B Streptococcus.

PMID: 12559788, UI: 22448533

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Vaccine 2003 Mar 7;21(11-12):1099-102
 

Vaccination of puppies with a lipid-formulated plasmid vaccine protects against a severe canine distemper virus challenge.

Fischer L, Tronel JP, Minke J, Barzu S, Baudu P, Audonnet JC

Merial SAS, Biological Discovery Research, 254 rue Marcel Merieux, 69007, Lyon, France

[Medline record in process]
 

We assessed whether the formulation of a DNA vaccine expressing the canine distemper virus (CDV) hemagglutinin (HA) and fusion (F) immunogens with the cationic lipid DMRIE-DOPE could induce serological responses and protection against a severe CDV challenge in the dog. Although clear protection was observed in dogs vaccinated with formulated plasmids only limited CDV specific antibody titers were observed in protected dogs before challenge, suggesting that protection could be explained by cell-mediated immunity and/or by a strong antibody-based memory response (priming) triggered by the infectious challenge. The high level of protection achieved in this study, demonstrated that formulated DNA CDV vaccines can generate in dogs a level a protection comparable to conventional CDV vaccines.

PMID: 12559786, UI: 22448531

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Vaccine 2003 Mar 7;21(11-12):1094-8
 

Seroprevalence of meningococcal serogroup C bactericidal antibody in England and Wales in the pre-vaccination era.

Trotter C, Borrow R, Andrews N, Miller E

Immunisation Division, PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, NW9 5EQ, London, UK

[Medline record in process]
 

Sera from an age-stratified sample of 1689 individuals, submitted to the PHLS Seroepidemiology Unit between 1996 and 1999 were tested for serum bactericidal antibodies to serogroup C meningococci. Titres decreased during infancy, presumably as maternal antibody waned, and increased in older teenagers, the peak age of meningococcal carriage. The prevalence of antibody titres greater than or equal to 8 was highest in adults, with an average of 25% of adults 25 years old or above with titres above this putative protective level. In the absence of vaccination, antibody may be generated from periods of carriage of serogroup C meningococci, from other meningococcal strains sharing non-capsular antigens, and other cross-reactive organisms. The inverse relationship between disease incidence and the prevalence of 'protective' antibody titres as described by Goldschneider et al. appears more consistent with a titre of >/=8 rather than >/=128, although the proportions 'protected' are much lower here than in Goldschneider's study. This study provides baseline antibody levels which will facilitate the evaluation of the meningococcal serogroup C conjugate vaccination programme.

PMID: 12559785, UI: 22448530

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Vaccine 2003 Mar 7;21(11-12):1052-9
 

Vaccination against type F botulinum toxin using attenuated Salmonella enterica var Typhimurium strains expressing the BoNT/F H(C) fragment.

Foynes S, Holley JL, Garmory HS, Titball RW, Fairweather NF

Department of Biological Sciences, Centre for Molecular Microbiology, Imperial College for Science, Technology and Medicine, Exhibition Road, SW7 2AZ, London, UK

[Medline record in process]
 

The utility of the htrA, pagC and nirB promoters to direct the expression of the carboxy-terminal (H(C)) fragment of botulinum toxin F (FH(C)) in Salmonella enterica var Typhimurium has been evaluated. Only low levels of serum antibody were induced after immunisation, and some protection against botulinum toxin type F was demonstrated after oral immunisation of mice with two doses of any of these recombinant Salmonella. Immunisation with two doses of recombinant Salmonella expressing FH(C) from the htrA promoter gave the greatest protection, against up to 10,000 mouse lethal doses of botulinum toxin type F. These results demonstrate the feasibility of an orally delivered vaccine against botulinum toxin type F.

PMID: 12559779, UI: 22448524

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Vaccine 2003 Mar 7;21(11-12):1044-7
 

MMR vaccination advice over the Internet.

Schmidt K, Ernst E

Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, EX2 4NT, Exeter, UK

[Medline record in process]
 

We wanted to investigate what advice UK homeopaths, chiropractors and general practitioners give on measles, mumps and rubella vaccination programme (MMR) vaccination via the Internet. Online referral directories listing e-mail addresses of UK homeopaths, chiropractors and general practitioners and private websites were visited. All addresses thus located received a letter of a (fictitious) patient asking for advice about the MMR vaccination. After sending a follow-up letter explaining the nature and aim of this project and offering the option of withdrawal, 26% of all respondents withdrew their answers. Homeopaths yielded a final response rate (53%, n=77) compared to chiropractors (32%, n=16). GPs unanimously refused to give advice over the Internet. No homeopath and only one chiropractor advised in favour of the MMR vaccination. Two homeopaths and three chiropractors indirectly advised in favour of MMR. More chiropractors than homeopaths displayed a positive attitude towards the MMR vaccination. Some complementary and alternative medicine (CAM) providers have a negative attitude towards immunisation and means of changing this should be considered.

PMID: 12559777, UI: 22448522

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Vaccine 2003 Feb 14;21(9-10):1006-22
 

Investigation of several selected adjuvants regarding their efficacy and side effects for the production of a vaccine for parakeets to prevent a disease caused by a paramyxovirus type 3.

Beck I, Gerlach H, Burkhardt E, Kaleta EF

Institute for Avian Diseases, Justus Liebig University Giessen, Frankfurter Strasse 91-93, D-35392, Giessen, Germany

[Medline record in process]
 

The infection with paramyxovirus type 3 (PMV-3) of parakeets can lead to severe illness in small psittacines (Neophema spp. and other parakeets) as well as in passerines (finches). The disease is characterized by acute or chronical pancreatitis and central nervous symptoms, such as torticollis as well as walking in circles and by high mortality rates in the affected flocks. As there is no licensed vaccine for psittacines available to prevent this disease. The aim of the following study was to find a suitable vaccine formulation for parakeets with inactivated PMV-3 and a well-tolerated and effective adjuvant. Seven adjuvants have been examined in ovo and in vivo regarding their efficacy and side effects. In these investigations, the classical Freund's complete Adjuvant (FCA) and Freund's incomplete Adjuvant (FICA) and Alhydrogel((R)), but also the more recent developments TiterMax((R)) Gold, Specol, Gerbu Adjuvant 100, and Diluvac((R)) Forte have been used. Regarding its efficacy and side effects, the vaccine formulation "PMV-3/Specol" has been evaluated positively and can be recommended for the production of a PMV-3 vaccine for parakeets.

PMID: 12547615, UI: 22436464

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Vaccine 2003 Feb 14;21(9-10):997-1005
 

A non-toxic lectin for antigen delivery of plant-based mucosal vaccines.

Medina-Bolivar F, Wright R, Funk V, Sentz D, Barroso L, Wilkins TD, Petri W, Cramer CL

Fralin Biotechnology Center, Virginia Polytechnic Institute and State University (Virginia Tech), 24061-0346, Blacksburg, VA, USA

[Medline record in process]
 

RicinB, the non-toxic galactose/N-acetylgalactosamine-binding subunit of ricin, was fused to a model antigen, green fluorescent protein (GFP), and expressed in tobacco plants and hairy root cultures to test for utility in mucosal vaccine delivery/adjuvancy. The fusion protein retained both GFP fluorescence and galactose/galactosamine-binding activity. Intranasal immunization of mice with galactosamine-affinity purified ricinB:GFP recovered from tobacco root cultures triggered significant increases in GFP-specific serum IgGs. This strong humoral response was comparable to that observed following GFP immunization with cholera toxin adjuvant. GFP at the same concentrations but without an adjuvant was non-immunogenic. Induction of higher levels of IgG(1) than IgG(2a) following ricinB:GFP immunization suggested the presence of a Th2 response. Serum and fecal anti-GFP IgA were also induced by immunization with ricinB:GFP. Our data suggest that ricinB can be used as an adjuvant and antigen carrier to the mucosa and is efficient in eliciting systemic and mucosal immune responses.

PMID: 12547614, UI: 22436463

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Vaccine 2003 Feb 14;21(9-10):977-82
 

Evaluation of adjuvants for protein vaccines against tuberculosis in guinea pigs.

Hogarth PJ, Jahans KJ, Hecker R, Hewinson RG, Chambers MA

Department of Bacterial Diseases, TB Research Group, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, KT15 3NB, Surrey, UK

[Medline record in process]
 

Subunit vaccines against tuberculosis show promise but require administration with adjuvants to stimulate relevant immune responses for protection. Guinea pigs are the model of choice for evaluating protective immunity to aerogenic challenge with virulent mycobacteria, but few studies have been undertaken to identify suitable adjuvants for vaccine screening in this species. Here, we compare the efficacy of several adjuvants to induce T cell responses to culture filtrate protein in guinea pigs. We report that of several adjuvants tested, the most promising was CpG ODN formulated in an aqueous emulsion. This adjuvant induced type 1 T cell responses equivalent to that of FIA, as measured by delayed-type hypersensitivity reactions (DTH), antigen-specific T cell proliferation and antigen-specific IgG1 and IgG2 responses. These data demonstrate the potential for CpG motif based adjuvants for use in TB vaccine screening in guinea pigs, and other diseases where a type 1 T cell response is required.

PMID: 12547611, UI: 22436460

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Vaccine 2003 Feb 14;21(9-10):946-9
 

Intranasal vaccination with ISCOMATRIX((R)) adjuvanted influenza vaccine.

Coulter A, Harris R, Davis R, Drane D, Cox J, Ryan D, Sutton P, Rockman S, Pearse M

CSL Limited, 45 Poplar Road, Vic. 3052, Parkville, Australia

[Medline record in process]
 

Mucosal delivery of inactivated vaccines that are able to elicit protective immune responses against respiratory diseases has been a long time goal of vaccinologists. Such vaccines would enable a more appropriate means of vaccination against respiratory diseases than those currently delivered by a parenteral route. The intranasal delivery of inactivated influenza vaccine plus the ISCOMATRIX((R)) (IMX) adjuvant, simply mixed together, was able to induce serum haemagglutination inhibition (HAI) titres in mice far superior to those obtained with unadjuvanted vaccine delivered subcutaneously. Furthermore, the IMX adjuvanted vaccine delivered intranasally induced mucosal IgA responses in the lung, nasal passages and large intestine, together with high levels of serum IgA. Intranasal delivery of IMX adjuvanted influenza vaccine in sheep gave antibody responses in both serum and nasal secretions that surpassed the levels obtained with unadjuvanted vaccine administered subcutaneously. These observations suggest that it may be possible to induce effective immunity to influenza in humans by intranasal vaccination with an IMX adjuvanted inactivated vaccine.

PMID: 12547607, UI: 22436456

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Vaccine 2003 Feb 14;21(9-10):940-5
 

Effect of priming on subsequent response to inactivated influenza vaccine.

Potter CW, Jennings R

Section of Infection and Immunity, Division of Genomic Medicine, University of Sheffield Medical School, S10 2RX, England, Sheffield, UK

[Medline record in process]
 

Although shown to be a potent stimulator of serum antibody responses in animal models, the adjuvant immuno-stimulating complexes (ISCOMs) showed little adjuvant effect for inactivated influenza vaccines in a volunteer study. The result may be the non-comparability of the studies: animal studies were carried out chiefly in unprimed mice, while volunteers are mostly primed by previous infection and/or immunization. To test this, Balb/C mice were infected with influenza viruses or immunized with inactivated influenza vaccine, and subsequently given inactivated vaccine in saline or incorporated into ISCOMs. The serum in antibody responses was measured 1 month after immunization. The results confirm the adjuvant activity of ISCOM in unprimed mice, and show a marked reduction in adjuvant activity for primed mice. We argue that ISCOMs are important to prime the T cell response necessary for the serum antibody response to saline vaccine, but largely unnecessary where priming has been accomplished by prior exposure to influenza antigens. Further, the value of ISCOMs may lie in promoting antibody responses in unprimed subjects, and not in enhancing antibody titres.

PMID: 12547606, UI: 22436455

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Vaccine 2003 Feb 14;21(9-10):902-14
 

Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins.

Mitchell JA, Green TD, Bright RA, Ross TM

Department of Microbiology and Immunology, School of Medicine, East Carolina University, Brody Health Sciences Building, Room 5N/96E, 600 Moye Boulevard, 27858-4354, Greenville, NC, USA

[Medline record in process]
 

Cross-protection between different subtypes of influenza A virus has been attributed to heterosubtypic immunity (HSI). Although, HSI can occur in the absence of anti-HA or anti-NA antibodies, HSI seems to be mediated, in part, by cross-reactive antibodies. In this study, we examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine C3d of complement (HA-mC3d(3)). HA-mC3d(3) elicited heterosubtypic immunity more efficiently than non-fused forms of HA and protected mice from lethal challenge of influenza with different subtypes. Plasmid encoding for various forms of HA were constructed from two influenza strains, A/Puerto Rico/8/34 (H1N1) or A/Aichi/2/68-x31 (H3N2). Vaccinated mice were analyzed for enhancement of anti-HA titers, affinity maturation of antibody, hemagglutinin-inhibition activity, and altered cytokine profiles. The HA-mC3d(3)-DNA vaccinated mice were protected from heterologous influenza challenge, even though sera from these mice had no viral-neutralizing activity against heterologous virus.

PMID: 12547601, UI: 22436450

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Vaccine 2003 Feb 14;21(9-10):869-76
 

Dendritic cell KLH loading requirements for efficient CD4(+) T-cell priming and help to peptide-specific cytotoxic T-cell response, in view of potential use in cancer vaccines.

Millard AL, Ittelet D, Schooneman F, Bernard J

Unite de Therapie Cellulaire, Institut Jean-Godinot, 1 Avenue du General Koenig, 51056 Cedex, Reims, France

[Medline record in process]
 

This study focuses on a Keyhole Limpet Hemocyanin (KLH) adjuvant strategy to augment efficacy of dendritic cell-based vaccines that use class I-restricted peptides. Requirements for loading dendritic cells (DC) with KLH were first determined in order to optimally prime CD4(+) T cells. These KLH-loaded cells were pulsed with antigenic peptide and cultured with T cells to induce a cytotoxic T lymphocyte (CTL) response against the peptide. Such a concomitant presentation of KLH and peptide by the same DC strongly augmented the peptide-specific CTL response, as compared to the response induced by DC pulsed with the peptide alone. This adjuvant effect was more pronounced for poorly immunogenic antigens. The use of optimised peptide and KLH-loaded DC may improve the efficacy of therapeutic anti-tumour peptide vaccination.

PMID: 12547596, UI: 22436445

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Vaccine 2003 Feb 14;21(9-10):849-55
 

Analysis of the role of vaccine adjuvants in modulating dendritic cell activation and antigen presentation in vitro.

Sun H, Pollock KG, Brewer JM

Department of Immunology and Bacteriology, University of Glasgow, Western Infirmary, G11 6NT, Glasgow, UK

[Medline record in process]
 

We have studied the effects of adjuvant formulations on the activation and antigen-presenting functions of bone marrow-derived dendritic cells (DCs). While LPS could induce high-level expression of MHC Class II and co-stimulator molecules on DCs, it did not enhance antigen presentation to co-stimulation independent DO11.GFP T hybridoma cells. In contrast, alum, NISV and PLGA formulations failed to activate DCs, but NISV and PLGA could enhance antigen-presentation efficiency by 10-100-fold. Irrespective of the previously described antigen release characteristics of each adjuvant, antigen presentation peaked at 6h and waned thereafter for all formulations. Given the importance of DCs in the activation of nai;ve T cell responses, these studies suggest that as yet undefined pathways of DC activation in vivo may underlie the activity of alum, PLGA and NISV adjuvants. Furthermore, as NISV and PLGA do not appear to act as slow-release systems in DCs, the ability of these particulate systems to induce high levels of antigen presentation by DCs probably has a more significant role in their adjuvant activity.

PMID: 12547593, UI: 22436442

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Vaccine 2003 Feb 14;21(9-10):843-8
 

Low effectiveness of DNA vaccination against HER-2/neu in ageing.

Provinciali M, Smorlesi A, Donnini A, Bartozzi B, Amici A

Laboratory of Tumor Immunology, INRCA Gerontology Research Department, Immunology Centre, Via Birarelli 8, 60121, Ancona, Italy

[Medline record in process]
 

We evaluated the effectiveness of vaccination with a HER-2/neu DNA plasmid to induce protective immunity against HER-2/neu overexpressing syngeneic TUBO tumour cells in old ages. Young and old Balb/c mice received three immunizations with a pCMVneuNT DNA plasmid and, successively, were challenged with TUBO cells. Young mice were completely protected whereas less than 60% protection was observed in old mice. Anti-p185(neu) antibodies were found in the sera from both young and old immunized mice, even if antibody production was significantly higher in young in comparison with old mice. Similarly, higher anti-p185(neu) lymphocyte proliferation was induced in young than in old mice. No anti-p185(neu) cytotoxicity was found in lymphocytes from old animals. We conclude that anticancer DNA vaccination has a lower effectiveness in old than in young ages.

PMID: 12547592, UI: 22436441

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Vaccine 2003 Feb 14;21(9-10):829-31
 

Mechanisms of vaccine adjuvant activity: initiation and regulation of immune responses by vaccine adjuvants.

Schijns VE

Department of Vaccine Technology & Immunology R&D, Intervet International BV, P.O. Box 31, 5830 AA, Boxmeer, The Netherlands

[Medline record in process]
 

PMID: 12547589, UI: 22436438

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Vaccine 2003 Feb 14;21(9-10):827
 

Immunopotentiatiors in modern vaccines.

Schijns VE

Department of Vaccine Technology and Immunology R&D, P.O. Box 31, 5830 AA, Boxmeer, The Netherlands

[Medline record in process]
 

PMID: 12547588, UI: 22436437

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