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Clin Infect Dis 2003 Mar 1;36(5):638-44
 

Key issues for a potential human immunodeficiency virus vaccine.

Hu DJ, Vitek CR, Bartholow B, Mastro TD

HIV Vaccine Section, Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. djh9@cdc.gov

[Medline record in process]
 

A safe, effective, and affordable vaccine remains the best long-term hope for bringing the global human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic under control. Recent scientific developments have suggested that the first generation of HIV vaccines available for public health care use will likely be of low to moderate efficacy, compared with currently licensed vaccines for other diseases. Nevertheless, such "partially effective" HIV vaccines could provide considerable individual and public health benefits. A consultation was held in January 2002 to advise the Centers for Disease Control and Prevention (Atlanta, Georgia) about critical issues that need to be addressed in anticipation of the eventual licensure and availability of an HIV vaccine in the United States. The present article summarizes the major issues discussed at the consultation with regard to the potential use of a partially effective vaccine in HIV prevention programs in the United States and the activities that are needed to prepare for vaccine availability.

PMID: 12594646, UI: 22482194

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Clin Infect Dis 2003 Mar 1;36(5):622-9
 

Can Postexposure Vaccination against Smallpox Succeed?

Mortimer PP

Virus Reference Division, Central Public Health Laboratory, London, United Kingdom. pmortimer@phls.org.uk

[Medline record in process]
 

What can be achieved by the vaccination of individuals exposed to smallpox virus after release of the virus by bioterrorists? There exist several past sources of information on postexposure vaccination failures from which it may be inferred that prompt vaccination of contacts (i.e., individuals exposed to smallpox) often prevented smallpox altogether, that revaccination of previously vaccinated individuals at any time during the first week of the incubation period was largely protective, and that revaccination done even as late as the second week of the incubation period attenuated disease and prevented most deaths. Primary vaccination done within 4 days of exposure was also usually protective at least from serious illness. Modern contingency planning against the release of smallpox virus during a bioterrorist attack should therefore include the capacity for prompt tracing and (re)vaccination of all contacts. Because a growing majority of the population has never before been vaccinated against smallpox and, so, may be unreachable within 4 days, anticipatory vaccination of sections of the populations of potential target countries should be considered if the bioterrorist threat intensifies.

PMID: 12594644, UI: 22482192

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Infect Immun 2003 Mar;71(3):1608-10
 

Clostridium difficile Vaccine and Serum Immunoglobulin G Antibody Response to Toxin A.

Aboudola S, Kotloff KL, Kyne L, Warny M, Kelly EC, Sougioultzis S, Giannasca PJ, Monath TP, Kelly CP

Gastroenterology. Gerontology Divisions, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston. Acambis, Inc., Cambridge, Massachusetts. Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

[Medline record in process]
 

There is a strong association between serum antibody responses to toxin A and protection against Clostridium difficile diarrhea. A parenteral C. difficile toxoid vaccine induced very-high-level responses to anti-toxin A immunoglobulin G (IgG) in the sera of healthy volunteers. After vaccination, the concentrations of anti-toxin A IgG in the sera of all 30 recipients exceeded the concentrations that were associated with protection in previous clinical studies. Furthermore, the median concentration of serum anti-toxin A IgG in the test group was 50-fold higher than the previous threshold. These findings support the feasibility of using a vaccine to protect high-risk individuals against C. difficile-associated diarrhea and colitis.

PMID: 12595488, UI: 22483728

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Infect Immun 2003 Mar;71(3):1596-1598
 

Effect of Vaccination with Refined Components of the Organism on Infection of Mice with Mycobacterium leprae.

Ngamying M, Sawanpanyalert P, Butraporn R, Nikasri J, Cho SN, Levy L, Brennan PJ

National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand. Department of Microbiology, Yonsei University, Seoul, Republic of Korea. Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado.

[Record supplied by publisher]
 

Only native products of Mycobacterium leprae, whether cell wall, cytosol, or membrane derived, can confer protective immunity against challenge in the mouse footpad. Previously, recombinant proteins were shown to be ineffective. The cell wall skeleton-the mycolyl-arabinogalactan-peptidoglycan complex-devoid of proteins is not protective.

PMID: 12595485

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Infect Immun 2003 Mar;71(3):1491-6
 

Venezuelan Equine Encephalitis Virus-Vectored Vaccines Protect Mice against Anthrax Spore Challenge.

Lee JS, Hadjipanayis AG, Welkos SL

Virology Division. Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.

[Medline record in process]
 

Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis. The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed of a self-replicating RNA (replicon) containing all of the VEE virus nonstructural genes and a multiple-cloning site in place of the VEE structural genes. Four different anthrax vaccines were constructed by cloning the protective antigen (PA) gene from B. anthracis into the VEE vaccine vector. The anthrax vaccines were produced by assembling the vectors into propagation-deficient VEE replicon particles in vitro. A/J mice inoculated subcutaneously with three doses of the mature 83-kDa PA vaccine were completely protected from challenge with the Sterne strain of B. anthracis. Similar results were obtained with vaccines composed of the PA gene fused to either the B. anthracis secretory sequence or to a tissue plasminogen activator secretory sequence in three additional mouse strains. Mice were unprotected from challenge after inoculation with the carboxy-terminal 63-kDa PA vaccine. These results suggest that these VEE-vectored vaccines may be suitable as candidate vaccines against anthrax.

PMID: 12595467, UI: 22483707

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Infect Immun 2003 Mar;71(3):1416-1426
 

Geographical Structure of Diversity and Differences between Symptomatic and Asymptomatic Infections for Plasmodium falciparum Vaccine Candidate AMA1.

Cortes A, Mellombo M, Mueller I, Benet A, Reeder JC, Anders RF

Papua New Guinea Institute of Medical Research, Madang, MP511. Papua New Guinea Institute of Medical Research, Goroka, EHP441, Papua New Guinea. The Cooperative Research Centre for Vaccine Technology, Department of Biochemistry, La Trobe University, Melbourne, Victoria 3086, Australia.

[Record supplied by publisher]
 

Plasmodium falciparum apical membrane antigen 1 (AMA1) is a prime malaria vaccine candidate. Antigenic diversity within parasite populations is one of the main factors potentially limiting the efficacy of any asexual-stage vaccine, including one based on AMA1. The DNA coding for the most variable region of this antigen, domain I, was sequenced in 168 samples from the Wosera region of Papua New Guinea, including samples from symptomatic and asymptomatic infections. Neutrality tests applied to these sequences provided strong evidence of selective pressure operating on the sequence of ama1 domain I, consistent with AMA1 being a target of protective immunity. Similarly, a peculiar pattern of geographical diversity and the particular substitutions found were suggestive of strong constraints acting on the evolution of AMA1 at the population level, probably as a result of immune pressure. In addition, a strong imbalance between symptomatic and asymptomatic infections was detected in the frequency of particular residues at certain polymorphic positions, pointing to AMA1 as being one of the determinants of the morbidity associated with a particular strain. The information yielded by this study has implications for the design and assessment of AMA1-based vaccines and provides additional data supporting the importance of AMA1 as a malaria vaccine candidate.

PMID: 12595459

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Infect Immun 2003 Mar;71(3):1234-1241
 

Activation of Natural Killer T Cells by alpha-Galactosylceramide Impairs DNA Vaccine-Induced Protective Immunity against Trypanosoma cruzi.

Miyahira Y, Katae M, Takeda K, Yagita H, Okumura K, Kobayashi S, Takeuchi T, Kamiyama T, Fukuchi Y, Aoki T

Department of Molecular and Cellular Parasitology. Department of Respiratory Medicine. Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421. Department of Tropical Medicine and Parasitology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582. Department of Veterinary Sciences, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.

[Record supplied by publisher]
 

Innate immunity as a first defense is indispensable for host survival against infectious agents. We examined the roles of natural killer (NK) T cells in defense against Trypanosoma cruzi infection. The T. cruzi parasitemia and survival of CD1d-deficient mice exhibited no differences compared to wild-type littermates. NK T-cell activation induced by administering alpha-galactosylceramide (alpha-GalCer) to T. cruzi-infected mice significantly changed the parasitemia only in the late phase of infection and slightly improved survival when mice were infected intraperitoneally. The combined usage of alpha-GalCer and benznidazole, a commercially available drug for Chagas' disease, did not enhance the therapeutic efficacy of benznidazole. These results suggest that NK T cells do not play a pivotal role in resistance to T. cruzi infection. In addition, we found that the coadministration of alpha-GalCer with DNA vaccine impaired the induction of epitope-specific CD8(+) T cells and undermined the DNA vaccine-induced protective immunity against T. cruzi. Our results, in contrast to previous reports demonstrating the protective roles of NK T cells against other infectious agents, suggest that these cells might even exhibit adverse effects on vaccine-mediated protective immunity.

PMID: 12595437

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Infect Immun 2003 Mar;71(3):1155-1160
 

Expression and Immunogenicity of Mycoplasma hyopneumoniae Heat Shock Protein Antigen P42 by DNA Vaccination.

Chen YL, Wang SN, Yang WJ, Chen YJ, Lin HH, Shiuan D

Department of Medical Technology, Fooying University. Department of Biological Science and Biotechnology Center, National Sun Yat-Sen University. Section of Infectious Diseases, Kaohsiung Veteran General Hospital, Kaohsiung. Department of Life Science and Institute of Biotechnology, National Dong-Hwa University, Hualien, Taiwan, Republic of China.

[Record supplied by publisher]
 

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia, a chronic nonfatal disease affecting pigs of all ages. The goal of this study was to design DNA vaccines by constructing plasmid pcDNA3/P42, carrying the heat shock protein gene P42 of M. hyopneumoniae, and to evaluate the immune responses elicited in BALB/c mice. The expression of P42 was first examined in transfected NIH 3T3 cells by reverse transcription-PCR to ensure that the construct was functional. The humoral and cell-mediated immune responses induced by the plasmid were further evaluated in BALB/c mice through intramuscular injection. Both immunoglobulin G1 (IgG1) and IgG2a levels were 64 times those of the control groups during the first 8 weeks. The levels of interleukin-2 (IL-2), IL-4, and gamma interferon mRNAs in the immunized animals were elevated, and the proliferation of spleen cells was also enhanced in the immunized animals. The results indicate that pcDNA3/P42 DNA immunization induces both Th1 and Th2 immune responses. In addition, antiserum from the immunized animals was found to inhibit the growth of M. hyopneumoniae. The present study reveals that DNA vaccination could be a new strategy against infection by M. hyopneumoniae and may have potential for developing vaccines for other infectious diseases as well.

PMID: 12595427

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Infect Immun 2003 Mar;71(3):1147-54
 

Inhalational poisoning by botulinum toxin and inhalation vaccination with its heavy-chain component.

Park JB, Simpson LL

Department of Medicine. Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania.

[Medline record in process]
 

Botulinum toxin is the etiologic agent responsible for the disease botulism, which is characterized by peripheral neuromuscular blockade. Botulism is ordinarily encountered as a form of oral poisoning. The toxin is absorbed from the lumen of the gut to reach the general circulation and is then distributed to peripheral cholinergic nerve endings. However, there is a widespread presumption that botulinum toxin can also act as an inhalation poison, which would require that it be absorbed from the airway. Experiments have been done to show that both pure toxin and progenitor toxin (a complex with auxiliary proteins) are inhalation poisons. Interestingly, the data indicate that auxiliary proteins are not necessary to protect the toxin or to facilitate its absorption. When studied on rat primary alveolar epithelial cells or on immortalized human pulmonary adenocarcinoma (Calu-3) cells, botulinum toxin displayed both specific binding and transcytosis. The rate of transport was greater in the apical-to-basolateral direction than in the basolateral-to-apical direction. Transcytosis was energy dependent, and it was blocked by serotype-specific antibody. The results demonstrated that the holotoxin was not essential for the process of binding and transcytosis. Both in vivo and in vitro experiments showed that the heavy-chain component of the toxin was transported across epithelial monolayers, which indicates that the structural determinants governing binding and transcytosis are found in this fragment. The heavy chain was not toxic, and therefore it was tested for utility as an inhalation vaccine against the parent molecule. This fragment was shown to evoke complete protection against toxin doses of at least 10(4) times the 50% lethal dose.

PMID: 12595426, UI: 22483666

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Infect Immun 2003 Mar;71(3):1083-90
 

Enteral Immunization with Attenuated Recombinant Listeria monocytogenes as a Live Vaccine Vector: Organ-Dependent Dynamics of CD4 T Lymphocytes Reactive to a Leishmania major Tracer Epitope.

Saklani-Jusforgues H, Fontan E, Soussi N, Milon G, Goossens PL

Unite d'Immunophysiologie et Parasitisme Intracellulaire. Unite Toxines et Pathogenie Bacterienne, Institut Pasteur, Paris, France.

[Medline record in process]
 

Listeria monocytogenes is considered as a potential live bacterial vector, particularly for the induction of CD8 T cells. The CD4 T-cell immune response triggered after enteral immunization of mice has not yet been thoroughly characterized. The dynamics of gamma interferon (IFN-gamma)- and interleukin-4 (IL-4)-secreting CD4 T cells were analyzed after priming through intragastric delivery of an attenuated DeltaactA recombinant L. monocytogenes strain expressing the Leishmania major LACK protein; a peptide of this protein, LACK(158-173) peptide (pLACK), is a well-characterized CD4 T-cell target in BALB/c mice. Five compartments were monitored: Peyer's patches, mesenteric lymph nodes (MLN), spleen, liver, and blood. A single intragastric inoculation of DeltaactA-LACK-LM in BALB/c mice led to colonization of the MLN and spleen at a significant level for at least 3 days. Efficient priming of IFN-gamma-secreting pLACK-reactive CD4 T cells was observed in all tested compartments. Interestingly, IL-4-secreting pLACK-reactive CD4 T cells were detectable at day 6 or 7 only in blood and liver. The absence of translocation of viable bacteria through the intestinal epithelium after further DeltaactA-LACK-LM inoculations was concomitant with the absence of an increase in the level of IFN-gamma secreted by the MLN, blood, and splenic pLACK-reactive Th1 T cells, although the levels remained significantly above the basal level. No change in this population size was detected in the spleen. However, an increase in the number of intragastric inoculations had a clinical beneficial effect in L. major-infected BALB/c mice. L. monocytogenes thus presents the potential of an efficient vector for induction of CD4 T cells when administered by the enteral route.

PMID: 12595418, UI: 22483658

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J Immunol 2003 Mar 1;170(5):2599-604
 

Prime boost vaccination strategies: CD8 T cell numbers, protection, and Th1 bias.

Woodberry T, Gardner J, Elliott SL, Leyrer S, Purdie DM, Chaplin P, Suhrbier A

Queensland Institute of Medical Research, Cooperative Research Center for Vaccine Technology, Australian Center for International & Tropical Health & Nutrition, Brisbane, Australia. Bavarian Nordic Research Institute, Martinsried, Germany.

[Medline record in process]
 

Vaccination strategies involving priming with DNA and boosting with a poxvirus vector have emerged as a preferred combination for the induction of protective CD8 T cell immunity. Using IFN-gamma ELISPOT and a series of DNA plasmid, peptide, and modified vaccinia Ankara (MVA) vaccine combinations, we demonstrate that the DNA/MVA combination was uniquely able to enhance IFN-gamma secretion by Ag-specific CD8 T cells. However, CD8 T cell populations induced by DNA/MVA vaccination failed to show an enhanced capability to mediate protection in an IFN-gamma-independent influenza challenge model. The DNA/MVA vaccine strategy was also not unique in its ability to induce high numbers of CD8 T cells, with optimal strategies simply requiring the use of vaccine modalities that individually induce high numbers of CD8 T cells. These experiments argue that rivals to DNA/poxvirus vaccination strategies for the induction of optimal protective CD8 T cell responses are likely to emerge.

PMID: 12594287, UI: 22482643

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J Immunol 2003 Mar 1;170(5):2496-507
 

Long-Term Maintenance of gp120-Specific Immune Responses by Genetic Vaccination with the HIV-1 Envelope Genes Linked to the Gene Encoding Flt-3 Ligand.

Sailaja G, Husain S, Nayak BP, Jabbar AM

Department of Microbiology and Immunology, Emory University School of Medicine, Emory Vaccine Center at Yerkes, Atlanta, GA 30329.

[Medline record in process]
 

DNA vaccines target dendritic cells (DC) to induce Ag-specific immune responses in animals. Potent HIV-specific immunity could be achieved by efficient priming of the immune system by DNA vaccines. We investigated a novel DNA vaccine approach based on the role of growth factors in DC expansion and differentiation. To this end, we constructed chimeric genes encoding the HIV envelope glycoproteins physically linked to the extracellular domain of Fms-like tyrosine kinase receptor-3 ligand (FLex; a DC growth factor; both mouse (m)FLex and human (h)FLex). These chimeric gene constructs synthesized biologically active, oligomeric FLex:gp120 fusion proteins and induced DC expansion (CD11c(+)CD11b(+)) when injected i.v. into mice. This DC expansion is comparable to that achieved by FLex DNA encoding native FLex protein. When delivered intramuscularly as DNA vaccines, hFLex:gp120 induced high frequencies of gp120-specific CD8(+) T cells in the presence or absence of FLex DNA-induced DC expansion, but gp120 and mFLex:gp120 elicited only low to moderate levels of Ag-specific CD8(+) T cells. In contrast, mFLex:gp120 induced high levels of anti-gp120 Abs under identical conditions of DNA vaccination. However, the Ab levels in mice immunized with DNA vaccines encoding hFLex:gp120 and gp120 proteins were low without DC expansion, but reached high levels comparable to that elicited by mFLex:gp120 only after the second boost in the presence of DC expansion. Importantly, the gp120-specific CD8(+) T cells persisted at high frequency for 114 days (16 wk) after a booster injection. These experiments provide insight into the importance of modulating DC function in vivo for effective genetic vaccination in animals.

PMID: 12594275, UI: 22482631

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J Infect Dis 2003 Jan 15;187(2):320-5
 

Interleukin-2 Increases CD4+ lymphocyte numbers but does not enhance responses to immunization: results of A5046s.

Valdez H, Mitsuyasu R, Landay A, Sevin AD, Chan ES, Spritzler J, Kalams SA, Pollard RB, Fahey J, Fox L, Namkung A, Estep S, Moss R, Sahner D, Lederman MM

Case Western Reserve University and University Hospitals of Cleveland, Ohio 44106, USA. valdez.hernan@clevelandactu.org

To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses.

Publication Types:
 

• Clinical trial

PMID: 12552459, UI: 22439939

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J Infect Dis 2003 Jan 15;187(2):315-9
 

Priming of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cell responses by dendritic cells loaded with HIV-1 proteins.

Huang XL, Fan Z, Zheng L, Borowski L, Li H, Thomas EK, Hildebrand WH, Zhao XQ, Rinaldo CR Jr

Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.

Proteins may serve as ideal CD8(+) T cell immunogens for human immunodeficiency virus type 1 (HIV-1) if they can be delivered to and processed through the human leukocyte antigen class I pathway. This study shows that human blood monocyte-derived dendritic cells loaded with liposome-complexed HIV-1 proteins and matured with CD40 ligand can prime CD8(+) T cells to HIV-1 in vitro. Whole HIV-1 protein in liposome may be an effective immunogen for HIV-1 vaccine protocols.

PMID: 12552458, UI: 22439938

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JAMA 2003 Feb 19;289(7):844-5
 

Risk of cutaneous vaccinia from health care workers who receive smallpox vaccine.

Mermel LA

Division of Infectious Diseases, Rhode Island Hospital, Providence.

[Medline record in process]
 

Publication Types:
 

• Letter

PMID: 12588263, UI: 22477313

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JAMA 2003 Feb 19;289(7):844-5
 

Risk of cutaneous vaccinia from health care workers who receive smallpox vaccine.

Neff JM

Center for Children With Special Needs, Children's Hospital and Regional Medical Center, Seattle, Wash.

[Medline record in process]
 

Publication Types:
 

• Letter

PMID: 12588262, UI: 22477312

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MMWR Morb Mortal Wkly Rep 2003 Feb 7;52(5):88-9, 99
 

Smallpox Vaccine Adverse Events Monitoring and Response System for the first stage of the smallpox vaccination program.

[Medline record in process]
 

Smallpox vaccination of civilian volunteer health-care workers began on January 24, 2003. As of February 4, a total of 37 states and counties have received shipments of smallpox vaccine, and 18 states and counties have begun smallpox vaccination; no serious adverse events have been reported. To monitor the occurrence of adverse events associated with vaccination, both those expected on the basis of previous experience and possible new unexpected adverse events, CDC and state health departments have established the Smallpox Vaccine Adverse Events Monitoring and Response System. The system also will be used to monitor the effectiveness of contraindication screening, identify new contraindications, and coordinate the distribution of vaccinia immune globulin (VIG) and cidofovir to the civilian population. This notice describes the components of the system, delineates roles and responsibilities, and explains how data from the system will be compiled and communicated.

PMID: 12588007, UI: 22475385

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Pediatrics 2003 Feb;111(2):296-301
 

Polio extraimmunization in children younger than 2 years after changes in immunization recommendations.

Mell LK, Davis RL, Mullooly JP, Black SB, Shinefield HR, Zangwill KM, Ward JI, Marcy SM, Chen RT

Center for Health Studies, Group Health Cooperative, Seattle, Washington, USA.

OBJECTIVE: To investigate trends over time in polio extraimmunization among children in 4 large health maintenance organizations and to study the association with recent changes in polio immunization policy. METHODS: Using 176 169 children who were born after 1994 and enrolled for their first 2 years of life, we assessed rates and trends of polio extraimmunization in the Vaccine Safety Datalink project. We used logistic regression to test the association of extraimmunization with different polio immunization schedules and with sociodemographic characteristics and used Poisson regression to test changes in rates over time. RESULTS: Overall, 10.5% were extraimmunized for poliovirus; children on the all inactivated polio virus or sequential schedule were one half as likely as those on the all oral polio virus schedule to be extraimmunized by 2 years of age. There was a significant decrease in extraimmunization over time, with <5% of children born at the end of 1997 being extraimmunized, compared with >15% at the beginning of 1994. CONCLUSIONS: Poliovirus extraimmunization rates have fallen dramatically in association with the change-over to the all inactivated polio virus schedule.

Publication Types:
 

• Multicenter study

PMID: 12563054, UI: 22451114

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Vaccine 2002 Jul 26;20(23-24):3023-33
 

Plasmid DNA encoding the respiratory syncytial virus G protein protects against RSV-induced airway hyperresponsiveness.

Miller M, Cho JY, Baek KJ, Castaneda D, Nayar J, Rodriguez M, Roman M, Raz E, Broide DH

Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0635, USA.

Respiratory syncytial virus (RSV) is an important cause of childhood respiratory disease as well as exacerbations of asthma. Although previous studies have demonstrated that a DNA vaccine encoding the RSV G protein can inhibit RSV replication in mouse models of RSV infection, studies have not been performed to determine whether a DNA vaccine encoding the RSV G protein can protect against RSV induced mucus expression and airway hyperresponsiveness which was the focus of this study. The DNA-G vaccine we constructed significantly inhibited RSV viral replication, mucus expression, and importantly was associated with inhibition of RSV induced airway responsiveness.

PMID: 12126916, UI: 22127374

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Vaccine 2002 Jul 26;20(23-24):3014-22
 

CpG-containing oligodeoxynucleotides augment and switch the immune responses of cattle to bovine herpesvirus-1 glycoprotein D.

Rankin R, Pontarollo R, Gomis S, Karvonen B, Willson P, Loehr BI, Godson DL, Babiuk LA, Hecker R, van Drunen Littel-van den Hurk S

Veterinary Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3.

The adjuvanticity of a synthetic oligodeoxynucleotide containing unmethylated CpG motifs (CpG ODN) was determined in cattle. Calves were immunized with a truncated secreted version of glycoprotein D (tgD) of bovine herpes virus-1 (BHV-1) formulated with alum, CpG ODN, or a combination of both. BHV-1 tgD formulated with CpG ODN or with alum and CpG ODN induced a stronger and more balanced immune response than tgD in alum. This level of immunity was of sufficient magnitude to minimize weight loss and significantly reduce the duration of virus shedding after intranasal viral challenge. Local tissue reactions generated by CpG ODN were very mild and transient, whereas reactions induced by alum or a combination of CpG ODN and alum were moderate in severity and duration. These data demonstrate that CpG ODN causes minimal injection site reactions and yet acts as an effective adjuvant in cattle.

PMID: 12126915, UI: 22127373

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Vaccine 2002 Jul 26;20(23-24):2989-94
 

The epidemiology of invasive Streptococcus pneumoniae disease in Catalonia (Spain). A hospital-based study.

Dominguez A, Salleras L, Cardenosa N, Ciruela P, Carmona G, Martinez A, Torner N, Fuentes M

Direccion General de Salud Publica, Departament de Sanitat i Seguretat Social, Travessera de les Corts 131-159, 08028 Barcelona, Spain. angelad@dsss.scs.es

The aim of this study was to investigate the incidence of invasive pneumococcal disease (IPD) in Catalonia. A hospital-based incidence study of the period 1997-1999 was carried out by reviewing the isolations of Streptococcus pneumoniae obtained from normally sterile sites reported by the hospitals that voluntarily participate in the Microbiological Reporting System of Catalonia (MRSC), and those obtained by active retrospective surveillance of cases recorded by microbiology laboratories of the remaining hospitals. Cases of pneumonia were included only if the blood culture was positive. The age, sex and clinical presentation of each patient were recorded. The global incidence of hospital-based IPD was 10.5 per 100,000 persons-year, and was much higher in subjects <2 years of age (59.6) and in those aged > or = 65 years (27.9). In subjects > or = 65 years, bacteremic pneumococcal pneumonias were more frequent in the months from December to March than they were in children <2 years of age (P<0.0001). The global incidence of IPD (10.5 per 100,000 persons-year) is high in Catalonia, greater than that of meningococcal or Haemophilus influenzae invasive disease. In children <2 years, the incidence is nearly six times higher (59.6 per 100,000 persons-year) with pneumonias (rate of 26.2 per 100,000 persons-year) and non-focal bacteremias (rate of 22.1 per 100,000 persons-year) being especially frequent.

PMID: 12126912, UI: 22127370

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Vaccine 2002 Jul 26;20(23-24):2981-8
 

Serum-derived IgG1-mediated immune exclusion as a mechanism of protection against H. pylori infection.

Keenan J, Neal S, Allardyce R, Roake J

Department of Surgery, Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand. jacqui.keenan@chmeds.ac.nz

The induction of protective immunity against Helicobacter challenge in a murine model was found to correlate with the magnitude of IgG (serum and gastric lavage) responsiveness to intra-nasal (i.n.) immunisation. IgG1-secreting hybridoma backpacks in Helicobacter pylori (H. pylori)-infected mice revealed serum transudation into the stomach. A Lpp20-specific monoclonal antibody was associated with significantly reduced H. pylori colonisation. Histology revealed aggregates of the remaining H. pylori in these mice, suggesting a role for IgG1-mediated immune exclusion of the bacteria. In vitro immunogold electron microscopy supported this hypothesis, but also suggested that a threshold of H. pylori-specific antibody needs to be maintained if immune exclusion by the host is to overcome immune evasion by the bacteria.

PMID: 12126911, UI: 22127369

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Vaccine 2002 Jul 26;20(23-24):2964-71
 

Interspecific neisserial high molecular weight proteins able to induce natural immunity responses are strongly correlated with in vitro bactericidal activity.

Sanchez S, Troncoso G, Criado MT, Ferreiros C

Departamento de Microbiologia y Parasitologia, Facultad de Farmacia, Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain.

Human sera from healthy volunteers and patients convalescent from meningitis were used to search for widely cross-reactive antigens implicated in vivo protective responses. Using the type strain Neisseria meningitidis B16B6 and a wide variety of both N. meningitidis and N. lactamica strains, several cross-reactive antigens and bactericidal sera were found, although the cross-reactivity patterns did not correlate with bactericidal activity, a total correlation was found between bactericidal activity and reaction with one or two high molecular weight proteins (162 and 138 kDa), and a mouse serum against the purified proteins showed a high bactericidal activity. Our results suggest that the high molecular weight proteins found are immunogenic and cross-reactive, eliciting bactericidal responses during infection and as a result of natural immunity. These proteins should be taken into account in studies for future vaccine formulations.

PMID: 12126909, UI: 22127367

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Vaccine 2002 Jul 26;20(23-24):2957-63
 

In vitro induction of memory-driven responses against Neisseria meningitidis by priming with Neisseria lactamica.

Sanchez S, Troncoso G, Criado MT, Ferreiros C

Departamento de Microbiologia y Parasitologia, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Natural immunity against Neisseria meningitidis is acquired during childhood and youth through successive colonizations by commensal Neisseria, carrier N. meningitidis, and other bacterial genera sharing cross-reactive antigens with the meningococci. We have analyzed in mice the ability of Neisseria lactamica strains to induce immunological memory so that, upon a later contact with N. meningitidis, quickly raise protective responses against antigens that show cross-reactivity with meningococcal surface proteins. Sera obtained from mice immunized with N. lactamica and boosted with N. meningitidis were able to kill meningococci, with bactericidal activities variable depending on the immunizing strains used in the assays. Different mixtures of those sera resulted in higher killing activities, which agrees with the idea that successive colonizations by N. lactamica enhance the anti-meningococcal response. The existence of such outer membrane cross-reactive antigens has to be kept in mind when using outer membrane vesicle (OMV)-based anti-meningococcal vaccines because their use can affect colonization by N. lactamica and other species, hampering the natural mechanisms of acquisition of immunity to the meningococci, and leaving its ecological niche free for colonization by undesirable microorganisms.

PMID: 12126908, UI: 22127366

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Vaccine 2002 Jul 26;20(23-24):2933-41
 

Co-immunisation with a plasmid DNA cocktail primes mice against anthrax and plague.

Williamson ED, Bennett AM, Perkins SD, Beedham RJ, Miller J, Baillie LW

Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK. dewilliamson@dstl.gov.uk

The protective antigen (PA) of Bacillus anthracis and the V antigen of Yersinia pestis are potent immunogens and candidate vaccine sub-units. When plasmid DNA encoding either PA or V antigen was used to immunise the Balb/c mouse, a low serum IgG titre was detected (log (10)1.0 or less) which was slightly increased by boosting with plasmid DNA. However, when mice immunised with plasmid DNA were later boosted with the respective recombinant protein, a significant increase in titre (up to 100-fold) was observed. Mice primed with a combination of each plasmid and boosted with a combination of the recombinant proteins, were fully protected (6/6) against challenge with Y. pestis. This compared favourably with mice primed only with plasmid DNA encoding the V antigen and boosted with rV, which were partially protected (3/6) against homologous challenge or with mice primed and boosted with plasmid DNA encoding the V antigen which were poorly protected (1/6). Combined immunisation with the two plasmid DNA constructs followed by boosting with a combination of the encoded recombinant proteins enhanced the protective immune response to Y. pestis compared with priming only with plasmid DNA encoding the V antigen and boosting with rV. This enhancement may be due to the effect of CpG motifs known to be present in the plasmid DNA construct encoding PA.

PMID: 12126905, UI: 22127363

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Vaccine 2002 Jul 26;20(23-24):2899-905
 

Anti-HBs levels after hepatitis B immunisation depend on test reagents: routinely determined 10 and 100 IU/l seroprotection levels unreliable.

Heijtink RA, Schneeberger PM, Postma B, Crombach W

Department of Virology, Erasmus University Rotterdam, Rotterdam, The Netherlands. heijtink@viro.fgg.eur.nl

In a large series of post-vaccination samples we compared the result of three commercially available anti-HBs assays (AxSYM, Architect and Access) on the quantitation of anti-HBs after immunisation with Engerix-B (HBsAg/ad) and GenHevacB (HBsAg/ay) vaccine. Two of the assays (AxSYM, Architect: Abbott Laboratories) gave related but not identical results with HBsAg from different sources. The result of the third assay (Access, Beckman Coulter) was related to that of AxSYM and Architect only for GenHevacB anti-HBs but differed for Engerix-B anti-HBs (P<0.001). This vaccine dependent discrepancy was also observed with the Vidas anti-HBs assay (BioMerieux). An external WHO reference panel could harmonise geometric mean anti-HBs levels from the four assays for GenHevacB but not for Engerix-B vaccination sera. We conclude that the individually determined anti-HBs level (IU/l) strongly depend on the test reagents and the vaccine under study.

PMID: 12126900, UI: 22127358

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Vaccine 2002 Jul 26;20(23-24):2848-50
 

The cost of not implementing routine neonates immunization programmes in HBsAg high prevalence countries.

Chauvin P, Ekra D, Plotkin SA

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• Letter

PMID: 12126893, UI: 22127351

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