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J Immunol 2002 Nov 1;169(9):5347-57
 

Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy.

Tryniszewska E, Nacsa J, Lewis MG, Silvera P, Montefiori D, Venzon D, Hel Z, Parks RW, Moniuszko M, Tartaglia J, Smith KA, Franchini G

Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.

[Medline record in process]
 

A cohort of rhesus macaques with long-standing SIVmac251 infection (> or =5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly attenuated poxvirus vector (NYVAC) vaccine candidate expressing the SIVmac structural gag-pol-env (gpe) genes and a novel chimeric fusion protein derived from the rev-tat-nef (rtn) regulatory genes. Control groups consisted of mock-vaccinated macaques or animals treated only with IL-2. Vaccination significantly expanded both virus-specific CD4(+) and CD8(+) T cell responses, and IL-2 further increased the vaccine-induced response to an immunodominant Gag epitope. Following antiretroviral treatment interruption, the viral set point was significantly lower in vaccinated than in control macaques for at least 4 consecutive mo, and viral containment was inversely correlated with vaccine-induced, virus-specific CD4(+) and CD8(+) T cell responses. These data provide the proof of concept that therapeutic vaccination before cessation of ART may be a feasible approach in the clinical management of HIV-1 infection.

PMID: 12391256, UI: 22278675

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J Immunol 2002 Nov 1;169(9):5227-35
 

Tumor Cell Lysate-Pulsed Dendritic Cells Are More Effective Than TCR Id Protein Vaccines for Active Immunotherapy of T Cell Lymphoma.

Gatza E, Okada CY

Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48101. Division of Hematology and Oncology, University of Michigan and Veterans Administration Ann Arbor Health Care Systems, Ann Arbor, MI 48105.

[Medline record in process]
 

TCR Id protein conjugated to keyhole limpet hemocyanin (KLH) (TCR Id:KLH) and injected with a chemical adjuvant (QS-21) induces a protective, Id-specific immune response against the murine T cell lymphoma, C6VL. However, Id-based immunotherapy of C6VL has not demonstrated therapeutic efficacy in tumor-bearing mice. We report here that C6VL lysate-pulsed dendritic cells (C6VL-DC) vaccines display enhanced efficacy in both the prevention and the therapy of T cell lymphoma compared with TCR Id:KLH with QS-21 vaccines. C6VL-DC vaccines stimulated potent tumor-specific immunity that protected mice against lethal challenge with C6VL and significantly enhanced the survival of tumor-bearing mice. Tumor-specific proliferation and secretion of IFN-gamma indicative of a Th1-type immune response were observed upon ex vivo stimulation of vaccine-primed lymph node cells. Adoptive transfer of immune T cell-enriched lymphocytes was sufficient to protect naive recipients from lethal tumor challenge. Furthermore, CD8(+) T cells were absolutely required for tumor protection. Although C6VL-DC and control vaccines stimulated low levels of tumor-specific Ab production in mice, Ab levels did not correlate with the protective ability of the vaccine. Thus, tumor cell lysate-pulsed DC vaccines appear to be an effective approach to generate potent T cell-mediated immune responses against T cell malignancies without requiring identification of tumor-specific Ags or patient-specific Id protein expression.

PMID: 12391241, UI: 22278660

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J Immunol 2002 Nov 1;169(9):5217-26
 

Induction of specific immune responses by polycation-based vaccines.

Luhrs P, Schmidt W, Kutil R, Buschle M, Wagner SN, Stingl G, Schneeberger A

Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, and Intercell AG, Vienna, Austria. Department of Dermatology, University School of Medicine, Essen, Germany.

[Medline record in process]
 

The s.c injection of tumor Ag-derived, MHC class I-binding peptides together with cationic poly-amino acids (e.g., poly-L-arginine; pR) has been shown to protect animals against a challenge with tumor cells expressing the respective peptide(s). Given our only restricted knowledge about immunogenic tumor-associated peptides, we sought to determine whether this pR-based vaccination protocol would also induce protective cancer immunity if large proteins were used instead of peptide epitopes. We found that the intracutaneous administration of the model Ag beta-galactosidase (beta-gal) together with pR (referred to as pR-based protein vaccine; pR-PV) was significantly more potent in protecting mice against the growth of beta-gal-expressing RENCA cells than the protein alone. Coadministration of pR enhanced both the beta-gal-induced specific humoral and CD8 response. The protective effect required CD8(+), but neither CD4(+) T lymphocytes nor beta-gal-specific Abs. beta-Gal priming of protective CD8(+) T lymphocytes was found to be CD4(+) T cell-independent, to take place within the draining lymph nodes, and to be accomplished by day 5 after vaccination. Ablation of the injection sites as early as 1.5 h after pR-PV administration still led to protection in a large proportion of the animals, indicating that certain protein Ags administered intradermally in the context of polycations are quickly transported to the draining nodes, where they induce molecular and cellular events resulting in the helper-independent priming and expansion of Tc1 cells. However, optimal protection required the prolonged presence of the injection site, suggesting that pR-PV injection facilitates the formation of a cutaneous depot of Ag-charged cells capable of migration and T cell activation.

PMID: 12391240, UI: 22278659

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J Immunol 2002 Nov 1;169(9):4951-60
 

Efficient Priming of CD4(+) and CD8(+) T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways.

Rush C, Mitchell T, Garside P

Division of Infection and Immunity, Institute of Biomedical and Life Sciences, and Western Infirmary, Department of Immunology and Bacteriology, University of Glasgow, Glasgow, United Kingdom.

[Medline record in process]
 

The initial cellular events and interactions that occur following DNA immunization are likely to be key to determining the character and magnitude of the resulting immune response, and as such, a better understanding of these events could ultimately lead to the design of more effective pathogen-appropriate DNA vaccines. Therefore, we have used a variety of sensitive cell-based techniques to study the induction of adaptive immunity in vivo. We examined the efficacy of induction of Ag-specific CD4(+) and CD8(+) T cell responses in vivo by the adoptive transfer of fluorescently labeled Ag-specific TCR transgenic T cells and have demonstrated how such approaches can be used to study the effect of simple DNA construct manipulations on immunological priming. OVA-specific CD8(+) and CD4(+) T cells were activated and divided in vivo following immunization with DNA constructs that targeted OVA expression to different subcellular locations; however, the kinetics and degree of cell proliferation were dependent on the cellular location of the expressed protein. DNA vectors encoding cell-associated OVA resulted in greater CD8(+) T cell division compared with other forms of OVA. In contrast, soluble secreted OVA targeted to the classical secretory pathway enhanced division of CD4(+) T cells. Furthermore, the inclusion of mammalian introns to enhance protein expression increased the ability of poorly immunogenic forms of Ag to activate naive T cells, indicating that not only the location, but also the amount of Ag expression, is important for efficient T cell priming following DNA injection.

PMID: 12391208, UI: 22278627

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J Immunol 2002 Nov 1;169(9):4928-35
 

Systemic Administration of IL-15 Augments the Antigen-Specific Primary CD8(+) T Cell Response Following Vaccination with Peptide-Pulsed Dendritic Cells.

Rubinstein MP, Kadima AN, Salem ML, Nguyen CL, Gillanders WE, Cole DJ

Department of Surgery, Section of Surgical Oncology, Medical University of South Carolina, Charleston, SC 29425.

[Medline record in process]
 

The systemic administration of IL-2 can act as a potent adjuvant for T cell-directed vaccine strategies. However, not only is the administration of IL-2 potentially toxic, but recent evidence suggests that it may also paradoxically limit the duration and magnitude of the cytotoxic T cell response. A recently identified cytokine, IL-15, shares many properties with IL-2 and may provide a preferential means of augmenting T cell-directed vaccine responses. Although well characterized in vitro, there are few data on the ability of IL-15 to augment T cell-mediated responses in vivo. We therefore evaluated the ability of systemic IL-15 to function as a T cell adjuvant in a murine vaccine model. To establish a population of easily identifiable Ag-responsive T cells, naive CD8(+) (OT-1) T cells were first adoptively transferred into mice. Vaccination with peptide-pulsed dendritic cells induced a modest expansion of OT-1 T cells. The addition of systemic IL-15 for 7 days following vaccination resulted in a significant increase in the expansion of responding T cells in the PBL, spleen, and lymph nodes. Importantly, the responding T cells were cytotoxic and maintained a Tc1-biased phenotype. We did not observe either enhanced resistance to activation-induced cell death or preferential generation of memory T cells as a result of treatment with IL-15 compared with IL-2. These studies show for the first time that IL-15 is capable of augmenting the primary CD8(+) T cell response to vaccination and contribute to the basis for future experiments exploring the clinical role of IL-15.

PMID: 12391205, UI: 22278624

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J Immunol 2002 Nov 1;169(9):4905-12
 

Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines.

Zeng W, Ghosh S, Lau YF, Brown LE, Jackson DC

Cooperative Research Center for Vaccine Technology, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.

[Medline record in process]
 

In this study, we describe the synthesis of various lipopeptides based on the sequence of luteinizing hormone-releasing hormone (LHRH) and report on their abilities to induce Abs against this "self" hormone when inoculated into mice in the absence of additional adjuvant. The peptides consisted of a colinear CD4(+) T helper cell epitope from the L chain of influenza virus hemagglutinin and LHRH, which has B cell epitopes but no T cell epitopes present in its sequence. Lipids were attached either at the N terminus or between the T cell epitope and LHRH, in the approximate center of the peptide. The lipopeptide constructs displayed different solubilities and immunological properties that depended not only on the lipid content but also on the position of attachment of the lipids. Some of these constructs were highly immunogenic, inducing high titers of Ab, which were capable of efficiently sterilizing female mice when administered in saline by s.c. or intranasal routes. The most effective vaccines were highly soluble, contained the dipalmitoyl-S-glyceryl cysteine moiety, and had this lipid attached at the center of the molecule. The relative ability of the lipopeptides to induce an Ab response in the absence of external adjuvant was reflected by their ability to up-regulate the surface expression of MHC class II molecules on immature dendritic cells. These results demonstrate that the composition and position within peptide vaccines of self-adjuvanting lipid groups can influence the ability to induce the maturation of dendritic cells and, in turn, the magnitude of the resulting Ab response.

PMID: 12391202, UI: 22278621

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J Immunol 2002 Nov 1;169(9):4889-96
 

DNA vaccination breaks tolerance for a neo-self antigen in liver: a transgenic murine model of autoimmune hepatitis.

Djilali-Saiah I, Lapierre P, Vittozi S, Alvarez F

Service de Gastroenterologie, Departement de Pediatrie, Hopital Sainte-Justine, Montreal, Quebec, Canada.

[Medline record in process]
 

Understanding the pathogenesis of autoimmune hepatitis requires an animal model in which chronic progressive immune injury develops spontaneously or with minimal manipulations. The new transgenic mouse model proposed in this study is based on the hypothesis that infectious agents have the potential to initiate autoreactivity through molecular mimicry. A transgenic mouse expressing lymphocytic choriomeningitis virus nucleoprotein (NP) in a H-2(b) background developed liver injury when vaccinated with plasmids expressing NP as an intracellular or a secretory protein. Coinjection of plasmids coding for NP and IL-12 facilitated the induction of a Th1 phenotype as detected by a specific B lymphocyte response characterized by a predominance of IgG2 subclass anti-NP Abs. CTLs activated in peripheral lymphoid organs by DNA vaccination migrated to the periportal and lobular areas of the liver. Their presence was associated with a significant degree of cytolysis, as evidenced by elevated transaminases several weeks after immunization. As activated specific T lymphocytes proliferated in the periphery and caused cytolysis of target cells, this study suggests that autoimmune hepatitis can be triggered by molecular mimicry, and that local injury may not be essential to initiate autoreactivity in the liver.

PMID: 12391200, UI: 22278619

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J Immunol 2002 Nov 1;169(9):4778-87
 

Containment of simian immunodeficiency virus infection in vaccinated macaques: correlation with the magnitude of virus-specific pre- and postchallenge CD4(+) and CD8(+) T cell responses.

Hel Z, Nacsa J, Tryniszewska E, Tsai WP, Parks RW, Montefiori DC, Felber BK, Tartaglia J, Pavlakis GN, Franchini G

Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

[Medline record in process]
 

Macaques infected with the SIV strain SIVmac251 develop a disease closely resembling human AIDS characterized by high viremia, progressive loss of CD4(+) T cells, occurrence of opportunistic infection, cachexia, and lymphomas. We report in this study that vaccination with the genetically attenuated poxvirus vector expressing the structural Ags of SIVmac (NYVAC-SIV-gag, pol, env) in combination with priming with DNA-SIV-gag, env resulted in significant suppression of viremia within 2 mo after mucosal exposure to the highly pathogenic SIVmac251 in the majority of vaccinated macaques. The control of viremia in these macaques was long lasting and inversely correlated to the level of both pre- and postchallenge Gag-specific lymphoproliferative responses, as well as to the level of total SIV-specific CD4(+) T lymphocyte responses at the peak of acute viremia as detected by intracellular cytokine-staining assay. Viremia containment also correlated with the frequency of the immunodominant Gag(181-189)CM9 epitope-specific CD8(+) T cells present before the challenge or expanded during acute infection. These data indicate, for the first time, the importance of vaccine-induced CD4(+) Th cell responses as an immune correlate of viremia containment. The results presented in this work also further demonstrate the potential of a DNA-prime/attenuated poxvirus-boost vaccine regimen in an animal model that well mirrors human AIDS.

PMID: 12391187, UI: 22278606

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J Virol 2002 Nov 15;76(22):11659-11676
 

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV(gpe) Recombinant Vaccine Result in Gag-Specific CD8(+) T-Cell Responses in Mucosal Tissues of Macaques.

Stevceva L, Alvarez X, Lackner AA, Tryniszewska E, Kelsall B, Nacsa J, Tartaglia J, Strober W, Franchini G

Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892. Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102. Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-1890. Aventis-Pasteur, Toronto, Ontario, Canada M2R 3T4.

[Record supplied by publisher]
 

As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A(*)01 molecule to assess the capacity of the highly attenuated poxvirus NYVAC/simian immunodeficiency virus (SIV) SIV(gpe) vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIV(mac251) by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NYVAC/SIV(gpe) and the anamnestic response to SIV(mac251) at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIV(mac) Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigen-specific CD8(+) T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIV(mac251) challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8(+) T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.

PMID: 12388726

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J Virol 2002 Nov;76(22):11637-44
 

Identification of second-site mutations that enhance release and spread of vaccinia virus.

Katz E, Wolffe E, Moss B

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445.

[Medline record in process]
 

The spread of most strains of vaccinia virus in cell monolayers occurs predominantly via extracellular enveloped virions that adhere to the tips of actin-containing microvilli and to a lesser extent via diffusion of released virions. The mechanism by which virions adhere to the cell surface is unknown, although several viral proteins may be involved. The present investigation was initiated with the following premise: spontaneous mutations that increase virus release will be naturally selected by propagating a virus unable to spread by means of actin tails. Starting with an A36R deletion mutant that forms small, round plaques, five independent virus clones with enhanced spread due to the formation of comet or satellite plaques were isolated. The viral membrane glycoprotein genes of the isolates were sequenced; four had mutations causing C-terminal truncations of the A33R protein, and one had a serine replacing proline 189 of the B5R protein. The comet-forming phenotype was specifically reproduced or reversed by homologous recombination using DNA containing the mutated or natural sequence, respectively. Considerably more extracellular enveloped virus was released into the medium by the second-site mutants than by the parental A36R deletion mutant, explaining their selection in tissue culture as well as their comet-forming phenotype. The data suggest that the B5R protein and the C-terminal region of the A33R protein are involved in adherence of cell-associated enveloped virions to cells. In spite of their selective advantage in cultured cells, the second-site mutants were not detectably more virulent than the A36R deletion mutant when administered to mice by the intranasal route.

PMID: 12388724, UI: 22276363

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J Virol 2002 Nov 15;76(22):11484-11490
 

Elicitation of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Mucosal Compartments of Rhesus Monkeys by Systemic Vaccination.

Baig J, Levy DB, McKay PF, Schmitz JE, Santra S, Subbramanian RA, Kuroda MJ, Lifton MA, Gorgone DA, Wyatt LS, Moss B, Huang Y, Chakrabarti BK, Xu L, Kong WP, Yang ZY, Mascola JR, Nabel GJ, Carville A, Lackner AA, Veazey RS, Letvin NL

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3005. New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772. Tulane Regional Primate Research Center, Covington, Louisiana 70433.

[Record supplied by publisher]
 

Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.

PMID: 12388710

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J Virol 2002 Nov;76(22):11447-59
 

Comparison of the complete DNA sequences of the oka varicella vaccine and its parental virus.

Gomi Y, Sunamachi H, Mori Y, Nagaike K, Takahashi M, Yamanishi K

Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa. The Research Foundation for Microbial Diseases of Osaka University. Department of Microbiology, Osaka University Medical School, Suita, Osaka, Japan.

[Medline record in process]
 

The DNA sequences of the Oka varicella vaccine virus (V-Oka) and its parental virus (P-Oka) were completed. Comparison of the sequences revealed 42 base substitutions, which led to 20 amino acid conversions and length differences in tandem repeat regions (R1, R3, and R4) and in an origin of DNA replication. Amino acid substitutions existed in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 52, 55, 59, 62, and 64. Of these, 15 base substitutions, leading to eight amino acid substitutions, were in the gene 62 region alone. Further DNA sequence analysis showed that these substitutions were specific for V-Oka and were not present in nine clinical isolates. The immediate-early gene 62 product (IE62) of P-Oka had stronger transactivational activity than the mutant IE62 contained in V-Oka in 293 and CV-1 cells. An infectious center assay of a plaque-purified clone (S7-01) from the V-Oka with 8 amino acid substitutions in ORF 62 showed smaller plaque formation and less-efficient virus-spreading activity than did P-Oka in human embryonic lung cells. Another clone (S-13) with only five substitutions in ORF 62 spread slightly faster than S7-01 but not as effectively as P-Oka. Moreover, transient luciferase assay in 293 cells showed that transactivational activities of IE62s of S7-01 and S7-13 were lower than that of P-Oka. Based on these results, it appears that amino acid substitutions in ORF 62 are responsible for virus growth and spreading from infected to uninfected cells. Furthermore, the Oka vaccine virus was completely distinguishable from P-Oka and 54 clinical isolates by seven restriction-enzyme fragment length polymorphisms that detected differences in the DNA sequence.

PMID: 12388706, UI: 22276345

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Lancet 2002 Oct 12;360(9340):1178
 

Change from oral poliovirus vaccine to inactivated poliovirus vaccine.

Mele A, Jefferson T, Franco E, Salmaso S

Dipartimento di Sanita Pubblica e Specializzazione di Igiene e Medicina Preventiva, Universita di Roma Tor Vergata, Rome, Italy

[Medline record in process]
 

PMID: 12387987, UI: 22276451

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Pediatr Infect Dis J 2002 Oct;21(10):961-70
 

The potential of pneumococcal conjugate vaccines for children.

Whitney CG, Pickering LK

Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Cwhitney@cdc.gov

[Medline record in process]
 

In contrast to earlier pneumococcal vaccines, conjugate vaccines hold promise for reducing pneumococcal morbidity and mortality in infants and young children. The first commercially available conjugate vaccine formulation, which targets seven serotypes, was licensed in the US and other countries in 2000; this vaccine is now part of routine infant immunization in the US. Demand has been high and greater than vaccine supply. Clinical trials indicate that conjugate vaccines are highly efficacious against invasive pneumococcal disease and modestly efficacious against otitis media and pneumonia. In carriage studies conjugate vaccines reduced vaccine-type carriage but led to an increase in carriage of other serotypes. Remaining questions include whether less frequent transmission of vaccine serotypes will mean less disease in unvaccinated children and adults or if nonvaccine serotypes will begin to cause more disease. Monitoring disease burden after widespread use in the US is critical for understanding the effects of the vaccine. In addition making pneumococcal vaccines available for children in developing countries should be a high priority.

PMID: 12394822, UI: 22282235

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Pediatr Infect Dis J 2002 Oct;21(10):940-7
 

Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine.

Obaro SK, Enwere GC, Deloria M, Jaffar S, Goldblatt D, Brainsby K, Hallander H, McInnes P, Greenwood BM, McAdam KP

Imperial College School of Medicine, London, United Kingdom.

[Medline record in process]
 

BACKGROUND: Pneumococcal polysaccharide/protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and type b (TETRAMUNE). METHODS: Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. RESULTS: Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV ( P< 0.00001 for Doses 1 and 2 and P< 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, >or=38 degrees C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 microg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 microg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 microg/ml (95% CI 14.7, 21.9; P= 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P= 0.02). However, all vaccinees achieved protective antibody values. CONCLUSION: The combination of TETRAMUNE and PnCV is safe and immunogenic.

PMID: 12394817, UI: 22282230

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Pediatr Infect Dis J 2002 Oct;21(10):927-31
 

Varicella-related hospitalizations in the vaccine era.

Ratner AJ

[Medline record in process]
 

BACKGROUND AND AIM Varicella is normally a self-limited disease of childhood that does not require hospitalization. In the prevaccine era varicella caused >9000 hospitalizations per year. To determine whether the varicella vaccine, licensed in 1995, has decreased hospitalizations because of varicella, we examined national rates of varicella-related hospital discharges (VRHD) covering a 12-year period that included pre- and postvaccine data.METHODS Data from the 1988 to 1999 National Hospital Discharge Survey and population estimates from the National Center for Health Statistics were used to calculate biennial rates of VRHD. To control for coding consistency, rates of invasive disease caused by were calculated for the same time period.RESULTS The rate of VRHD for 1998 to 1999 (4.42 hospitalizations per 100 000 person-years) was the lowest of any of the periods measured, but this difference was not statistically significant. The same was true of VRHD limited to cases with varicella coded as the primary diagnosis. A trend toward a decrease in VRHD was observed in all age groups examined, although none was statistically significant. Calculated rates from this national data set were in agreement with prior studies using active surveillance, and the previously documented fall in hospitalizations caused by invasive disease was demonstrated using these methods.CONCLUSIONS Although it is uncommon for children with varicella to require hospitalization, these cases are an important contributor to cost and morbidity of varicella. In contrast to predictions of prelicensure mathematical models, there has not been a significant decrease in total or first diagnosis VRHD since the vaccine became available. Current coverage levels are below those used in prelicensure models. Increased acceptance of the varicella vaccine by parents and practitioners may aid in the further decrease of varicella-related hospitalizations.

PMID: 12394814, UI: 22282227

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Science 2002 Oct 25;298(5594):725-7
 

Public health. Creeping consensus on SV40 and polio vaccine.

Ferber D

[Medline record in process]
 

Publication Types:
 

• News

PMID: 12399560, UI: 22287154

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Vaccine 2002 Nov 1;20(31-32):3783
 

Corrigendum to "Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL((R)) adjuvant" [Vaccine 20 (2002) 3292-3303].

Skeiky YA, Coler RN, Brannon M, Stromberg E, Greeson K, Thomas Crane R, Webb JR, Campos-Neto A, Reed SG

Corixa Corporation, 1124 Columbia Street, Suite 200, 98104, Seattle, WA, USA

[Medline record in process]
 

PMID: 12399210, UI: 22287266

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Vaccine 2002 Nov 1;20(31-32):3778-82
 

Prior meningococcal A/C polysaccharide vaccine does not reduce immune responses to conjugate vaccine in young adults.

Lakshman R, Burkinshaw R, Choo S, Finn A

Sheffield Institute for Vaccine Studies, Sheffield Children's Hospital, S10 2TH, Sheffield, UK

[Medline record in process]
 

The immune responses induced in young adults by a meningococcal A/C polysaccharide-diphtheria toxoid conjugate vaccine (Mcj) and a meningococcal A/C plain polysaccharide vaccine (Mps) were evaluated in unvaccinated subjects and those who had received either vaccine previously. 195 subjects aged 17-30 years received either Mps or Mcj. After 12 months, they were randomised again to receive a second dose of either vaccine. Serogroup specific serum bactericidal assay (SBA) titers and IgG antibody responses were assayed before and 4-8 weeks after primary and booster immunisation. Both vaccines were immunogenic in previously unvaccinated subjects. Administration of a dose of Mps after previous Mps or Mcj induced lower bactericidal titers to group C Neisseria meningitidis than those seen after a single dose of Mps. Bactericidal antibody responses to Mcj were not reduced in subjects who had previously received Mps.

PMID: 12399209, UI: 22287265

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Vaccine 2002 Nov 1;20(31-32):3764-9
 

Development of a new vaccine delivery method for fish: percutaneous administration by immersion with application of a multiple puncture instrument.

Nakanishi T, Kiryu I, Ototake M

Laboratory of Fish Pathology, Department of Veterinary Medicine, Nihon University, 1866 Kameino, Fujisawa, 252-8510, Kanagawa, Japan

[Medline record in process]
 

A new administration method was developed for vaccination of juvenile rainbow trout against beta-haemolytic Streptococcus. This simple and convenient method was equal in effectiveness to intra-peritoneal injection. Small skin lesions were produced using a multiple puncture instrument while fish were immersed in a vaccine suspension containing formalin-killed Streptococcus iniae. Upon challenge 2 weeks after vaccination, mortality of fish vaccinated by this method was 40%, equal to that by intra-peritoneal injection, while non-vaccinated control fish and fish vaccinated by immersion (without multiple puncture) each experienced 80% mortality. High efficacy was obtained with the multiple puncture/immersion method even when vaccine was diluted 10-fold. Quantitative analysis using fluorescent microspheres revealed that both antigen uptake by skin and delivery to the kidney and spleen were more effective with this method than with immersion alone. Microspheres were found in the skin within the pinpoint lesions and pressure mark caused by multiple puncture instrument. The greater protection gained by the present method can be attributed to higher numbers of particulate antigens taken up by fish and delivered to the lymphoid tissues.

PMID: 12399207, UI: 22287263

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Vaccine 2002 Nov 1;20(31-32):3755-63
 

Evaluation of the murine immune response to Leishmania meta 1 antigen delivered as recombinant protein or DNA vaccine.

Serezani CH, Franco AR, Wajc M, Umada Yokoyama-Yasunaka JK, Wunderlich G, Borges MM, Uliana SR

Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1374, CEP 05508-900, Sao Paulo, Brazil

[Medline record in process]
 

The meta 1 gene of Leishmania is conserved across the genus and encodes a protein upregulated in metacyclic promastigotes. Meta 1 constitutive overexpressing mutants show increased virulence to mice. In this paper, both meta 1 recombinant protein and plasmids bearing the meta 1 gene were tested for their antigenicity and potential for inducing protective immunity in mice. Vaccination with the recombinant protein induced a predominant Th2-type of response and did not result in protection upon challenge with live parasites. Surprisingly, the expected reversal to a CD4(+) Th1-type of response upon genetic immunisation by the intramuscular route was not observed. Instead, vaccination with either the meta 1 gene alone or in fusion with the monocyte chemotactic protein (MCP)-3 cDNA induced a Th2-type of response that correlated with lack of protection against infection.

PMID: 12399206, UI: 22287262

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Vaccine 2002 Nov 1;20(31-32):3752-3754
 

The implication of a reduced-dose hepatitis B vaccination schedule in low risk newborns.

Lee SS, Young BW, Wong KH, Lim WL

Department of Health, Hong Kong SAR Government, Hong Kong, China

[Record supplied by publisher]
 

Five hundred and seventy-four babies born to HBsAg negative mothers in Hong Kong received either a regular (5&mgr;g) or reduced (2.5&mgr;g) three-dose regimen of recombinant hepatitis B vaccine. A significantly higher anti-HBs positivity rate (>/=10mIU/ml), geometric mean titer (GMT) and the maintenance of a high anti-HBs level (>/=100mIU/ml) were observed with the regular-dose regimen. The differences persisted, however, only up to 1 year post-vaccination. Over an 8-year period, only 1% of the vaccinees demonstrated anti-HBc seroconversion and none had become HBsAg positive. The long-term efficacy of the reduced-dose regimen was confirmed, even in an HBV endemic population.

PMID: 12399205

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Vaccine 2002 Nov 1;20(31-32):3739-3743
 

Protective efficacy of hepatitis B vaccine without HBIG in infants of HBeAg-positive carrier mothers in Thailand.

Lolekha S, Warachit B, Hirunyachote A, Bowonkiratikachorn P, West DJ, Poerschke G

Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Ramathabodi Hospital, Mahidol University, Bangkok, Thailand

[Record supplied by publisher]
 

The primary objective of this study was to estimate the efficacy of a recombinant hepatitis B vaccine (H-B-VAXII) in preventing chronic hepatitis B infection when given alone without concomitant hepatitis B immune globulin (HBIG) to healthy Thai infants born of HBeAg-positive carrier mothers. The infants received a 0.5ml (5&mgr;g HBsAg) intramuscular injection of H-B-VAXII either at birth, 1, and 6 months of age (Schedule A) or at birth, 1, 2, and 12 months of age (Schedule B). Blood drawings for the determination of hepatitis B virus (HBV) serologic markers were scheduled 4, 9, and 13 months following the initial dose of vaccine. At 13 months, 5 (10%) of 50 infants vaccinated on Schedule A and 7 (14.9%) of 47 infants vaccinated on Schedule B had experienced chronic HBV infection. Based on an expected infection rate in unimmunized infants of either 70 or 90%, the overall efficacy for both schedules combined was estimated to be 82.3% (95% CI: 70.6, 90.6) or 86.2% (95% CI: 77.1, 92.7), respectively. Corresponding schedule-specific estimates were for Schedule A: 85.7% (95% CI: 68.8, 95.3) or 88.9% (95% CI: 75.8, 96.3) and for Schedule B: 78.7% (95% CI: 59.6, 91.1) or 83.4% (95% CI: 68.6, 93.1). These results suggest that in areas of high endemicity, where mothers may not always be screened for HBV infection, routine vaccination of infants at birth with a course of hepatitis B vaccine alone should be highly protective, even for very high-risk infants of HBeAg-positive mothers.

PMID: 12399203

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Vaccine 2002 Nov 1;20(31-32):3725-3730
 

Anamnestic response to administration of purified non-adsorbed hepatitis B surface antigen in healthy responders to hepatitis B vaccine with long-term non-protective antibody titres.

Dentico P, Crovari P, Lai PL, Ponzio F, Safary A, Pellegrino A, Meurice F, Di Pasquale A, Tornieporth N, Volpe A, Icardi G

Department of Internal Medicine and Infectious Diseases, General Hospital of Bari, University of Bari, Piazza G Cesare 11, 70124, Bari, Italy

[Record supplied by publisher]
 

A clinical trial with four groups receiving either 0.6, 3.5, 10 or 20&mgr;g of purified non-adsorbed hepatitis B surface antigen (HBsAg) was performed to study the kinetics as well as the capacity of the immune memory to respond following exposure to HBsAg in responders to a complete course of hepatitis B vaccine, in whom anti-HBs titres had declined below the seroprotective level. The study population included 64 healthy individuals. All response parameters seropositivity, seroprotection rates, booster response rates and geometric mean titres (GMTs), consistently showed that the immune response was highly satisfactory and dose-dependent. A remarkable immune response was obtained even with a trace amount of HBsAg. This study further supports recent indication that booster hepatitis B vaccine doses may be unnecessary in healthy adult responders to a full course of hepatitis B vaccination.

PMID: 12399201

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Vaccine 2002 Nov 1;20(31-32):3720-4
 

Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users.

Amendola A, Tanzi E, Zappa A, Colzani D, Boschini A, Musher DM, Zanetti AR

Institute of Virology, University of Milan, Via Pascal 38, 20133, Milan, Italy

[Medline record in process]
 

The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples.Vaccinations were well-tolerated. The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels.Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.

PMID: 12399200, UI: 22287256

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Vaccine 2002 Nov 1;20(31-32):3709-19
 

A modified live Mycoplasma gallisepticum vaccine to protect chickens from respiratory disease.

Papazisi L, Silbart LK, Frasca S, Rood D, Liao X, Gladd M, Javed MA, Geary SJ

Department of Pathobiology and Veterinary Science, The University of Connecticut, Storrs, CT, USA

[Medline record in process]
 

The aim of this study was to assess the efficacy of a modified live Mycoplasma gallisepticum vaccine (GT5) for the protection of chickens against infection and respiratory disease. GT5 was constructed by the reconstitution of the avirulent high passage R (R(high)) strain with the gene encoding the major cytadhesin GapA. GT5 expressed GapA on its surface yet retained the phenotypic characteristics of the parental R(high) strain. Birds vaccinated with GT5 were protected upon challenge with the virulent low passage R (R(low)) strain as evidenced by a complete absence of tracheal lesions 2 and 4 weeks post-challenge, in contrast to sham immunized/challenged control birds. Modest amounts of IgG, and little, if any secretory IgA or IgM anti-M. gallisepticum were found in tracheal washings following vaccination. However, copious amounts of specific IgA were found following challenge, especially in sham immunized birds. This suggests that the tracheal IgG elicited by GT5 vaccination may have been responsible for blocking the initial colonization of R(low), thereby resulting in protection.

PMID: 12399199, UI: 22287255

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Vaccine 2002 Nov 1;20(31-32):3702-8
 

Optimization of DNA vaccination against cutaneous leishmaniasis.

Mendez S, Belkaid Y, Seder RA, Sacks D

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 126, Building 4, Center Dr. MSC 0425, 20892-0425, Bethesda, MD, USA

[Medline record in process]
 

The present studies were designed to examine the requirements of dose, route of inoculation and constituent antigens for the maintenance of complete and long lasting protection against cutaneous leishmaniasis due to Leishmania major conferred by a cocktail DNA vaccine encoding the Leishmania antigens LACK, LmST11 and TSA. Vaccination of C57Bl/6 mice with LACK DNA alone resulted in partial protection, whereas the combination of LmST11 and TSA provided stronger, though still incomplete protection compared to the combination of all three Ag DNAs. When intradermal (i.d), intramuscular (i.m.), and subcutaneous (s.c.) vaccination routes were compared, i.d. immunization reduced by five-fold the dose necessary to maintain complete protection. In vivo depletion of CD4+ or CD8+ T cells provided direct evidence that both populations are necessary to mediate complete protection. These results establish intradermal vaccination using DNA encoding multiple Leishmania antigens as a way to optimize priming of CD4+ and CD8+ T cells necessary for potent and durable protection against cutaneous leishmaniasis.

PMID: 12399198, UI: 22287254

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Vaccine 2002 Nov 1;20(31-32):3695-701
 

Immunogenicity of hepatitis B vaccines: implications of immune memory.

Koff RS

Department of Medicine, Division of Gastroenterology, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, 01655, Worcester, MA, USA

[Medline record in process]
 

The subunit recombinant hepatitis B virus (HBV) vaccines available in the US differ in hepatitis B surface antigen content. Clinical studies have linked higher antigen formulations with enhanced peak protective antibody levels. This is important for the elderly, smokers, the obese, and the immunocompromised. Immune memory, which is responsible for prolonged protection when HBV vaccine-induced antibody levels become undetectable, may be related to antigen persistence on immunologically active cells. Antigen persistence may be related to antigen content of the vaccine and thereby influences the duration of immunity. Proof of this concept will require additional studies of immune memory in HBV.

PMID: 12399197, UI: 22287253

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Vaccine 2002 Nov 1;20(31-32):3658-3667
 

Effect of monophosphoryl lipid A (MPL((R))) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM(197) conjugate vaccine in healthy toddlers.

Vernacchio L, Bernstein H, Pelton S, Allen C, MacDonald K, Dunn J, Duncan DD, Tsao G, LaPosta V, Eldridge J, Laussucq S, Ambrosino DM, Molrine DC

Department of Pediatrics, Harvard Medical School, 02115, Boston, MA, USA

[Record supplied by publisher]
 

As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL((R))) in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50&mgr;g of MPL((R)) with or without alum (AlPO(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL((R)) were well-tolerated and a dose-dependent effect of MPL((R)) on specific cellular responses was observed. The 10&mgr;g MPL((R)) dose significantly enhanced CRM(197)-specific T-cell proliferation (P=0.02) and interferon-gamma (INF-gamma) production (P=0.009) compared to responses of controls who received PCV9 with AlPO(4). In contrast, CRM(197)-specific T-cell proliferation and interferon-gamma production of the 50&mgr;g MPL((R))/AlPO(4) group were decreased when compared to controls although these differences did not reach statistical significance. IL-5 and IL-13 responses after immunization showed a similar pattern with increased production in the 10&mgr;g MPL((R)) group and decreased production in the 50&mgr;g MPL((R))/AlPO(4) group compared to controls. There were no differences in serum IgG antibody concentrations to the nine vaccine pneumococcal capsular polysaccharides and carrier protein between the MPL((R))-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL((R)) on T-helper cell type 1 (TH-1) responses to the carrier protein and also suggest an effect on T-helper cell type 2 (TH-2) responses.

PMID: 12399193

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Vaccine 2002 Nov 1;20(31-32):3644-9
 

The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population.

Jacques P, Moens G, Desombere I, Dewijngaert J, Leroux-Roels G, Wettendorff M, Thoelen S

Interdisciplinaire Dienst voor het Welzijn, IDEWE, Leuven, Belgium

[Medline record in process]
 

Approximately 5% of vaccinees display an inadequate response after the administration of the standard three dose hepatitis B vaccine. A new hepatitis B vaccine (HBsAg/AS04) formulated with the adjuvant AS04 which contains 3'-deacylated monophosphoryl lipid A (3D-MPL) and alum has been developed. AS04 enhances the immune response which may be beneficial to non-responders. In a single-blind, randomised study, we tested the immunogenicity and reactogenicity of the new vaccine with that of commercially established hepatitis B vaccine, both on a 0, 1, 6 months schedule in 20-60 years old non-responders (titre <10mIU/ml after four doses of hepatitis B vaccine). One month after the first dose the seroprotection rate was 44% for group 1 (58 subjects) receiving the established vaccine versus 66% for group 2 receiving HBsAg/AS04 (57 subjects) (P=0.03). One month after the second dose this was 58 and 81%, respectively (P<0.005) and 1 month after the third dose this was 68 and 98%, respectively (P<0.001). One month after each dose, GMTs were 34, 56 and 111mIU/ml for group 1 versus 123, 222 and 1937mIU/ml for the HBsAg/AS04 group (P<0.05, <0.01 and 0.0001, respectively). Pain at the injection site was the most commonly reported local symptom and very few symptoms were scored as severe. In this group of adult non-responders to previous hepatitis vaccination, the HBsAg/AS04 vaccine was well tolerated and induced, at all time-points, a superior immune response compared to the licensed hepatitis B vaccine.

PMID: 12399191, UI: 22287247

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Vaccine 2002 Nov 1;20(31-32):3638-43
 

Responses of varicella zoster virus (VZV)-specific immunity in seropositive adults after inhalation of inactivated or live attenuated varicella vaccine.

Terada K, Niizuma T, Ogita S, Kataoka N

Department of Pediatrics, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Okayama, Japan

[Medline record in process]
 

To examine boostering of varicella zoster virus (VZV)-specific immunity in seropositive adults after nasal inhalation of heat-inactivated or live attenuated varicella vaccine, we determined specific cellular immunity, IgG antibody in sera and secretory IgA antibody in saliva before and after the inhalation. The mean titers in specific IgG antibody and skin test findings significantly increased following inhalation of both vaccines. However, the ratio of a two-fold or more increase in the levels of IgG antibody or skin test did not show significant difference after inhalation of the inactivated vaccine in comparison with those in the control. After inhalation of the live vaccine, the ratio showed significant difference but transmission of the live vaccine virus to others was suspected. No significant increase in VZV-secretory IgA antibody levels in saliva was noted following inhalation. The results of this study suggested that nasal inhalation of the live vaccine could increase specific immunity in adults. This method would be similar to the natural infection and simpler than subcutaneous injection.

PMID: 12399190, UI: 22287246

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Vaccine 2002 Nov 1;20(31-32):3632-4
 

Preadolescent non- and hyporesponders following three doses of hepatitis B vaccine need only one more dose.

Duval B, Boulianne N, De Serres G, De Wals P, Masse R, Trudeau G

Institut National de Sante Publique du Quebec, 2400 rue d'Estimauville, Que., G1E 7G9, Beauport, Canada

[Medline record in process]
 

A small proportion of healthy children fail to develop antibodies against hepatitis B after three doses of vaccine. Few data are available regarding the optimal re-immunization strategy. We measured the immune response 1 month after a single supplementary dose of recombinant hepatitis B vaccines in 18 young preadolescents who were non- or hyporesponsive after a regular primary course of three doses of recombinant hepatitis B vaccines. Among them, 100% seroconverted and 89% reached the seroprotective titer of 10milli-International Units (mIU)/ml. Most healthy children, particularly if they are hyporesponders, will have reached the seroprotective level after one dose and will not need further injections.

PMID: 12399188, UI: 22287244

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Vaccine 2002 Nov 1;20(31-32):3629-31
 

Field testing of Schistosoma japonicum DNA vaccines in cattle in China.

Shi F, Zhang Y, Lin J, Zuo X, Shen W, Cai Y, Ye P, Bickle QD, Taylor MG

Shanghai Institute of Animal Parasitology, Chinese Academy of Agricultural Sciences, 3 Lane 345 Shi-long Road, 200232, Shanghai, PR China

[Medline record in process]
 

Vaccines are needed to reduce the zoonotic reservoir of Schistosoma japonicum infection in bovines in China. We have developed two experimental DNA vaccines and have already shown these to be capable of inducing partial protection in water buffalo naturally exposed to the risk of S. japonicum infection in the field. We now report a similar field trial in cattle, the other major bovine reservoir host species in China. Groups of cattle were vaccinated with the VRSj28 vaccine or the VRSj23 vaccine, or, to test whether protection could be enhanced by combination vaccination, with both these DNA vaccines together. After vaccination, the cattle were exposed to natural infection in the field for a period of 54 days. Worm and egg counts carried out at the end of the experiment showed that each of the vaccine groups showed partial resistance, and that combined vaccination was not more effective than vaccination with the individual plasmids.

PMID: 12399187, UI: 22287243

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Vaccine 2002 Nov 1;20(31-32):3627-8
 

Yellow fever vaccine safety: a reality or a myth?

Arya SC

Centre for Logistical Research and Innovation, M-122, Greater Kailash-Part 2, 110048, New Delhi, India

[Medline record in process]
 

The 17D-derived yellow fever (YF) vaccines have had an excellent record of their safety among millions of recipients. Recently, extensive viral dissemination in seven vaccinees, aged 5-79 years, with just one survivor posed a serious challenge for vaccine manufacturers. Prospective evaluations of yellow fever vaccine bulk suspensions for their viscerotropism and neurovirulence in primates or an alternate animal should minimize identical viral dissemination among prospective recipients of YF vaccines.

PMID: 12399186, UI: 22287242

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