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Clin Infect Dis 2003 Jan 1;36(1):60-3
 

Management of rabies in humans.

Jackson AC, Warrell MJ, Rupprecht CE, Ertl HC, Dietzschold B, O'Reilly M, Leach RP, Fu ZF, Wunner WH, Bleck TP, Wilde H

Department of Medicine, Queen's University, Kingston, Ontario, Canada K7L 2V7. jacksona@post.queensu.ca

Rabies is a fatal disease in humans, and, to date, the only survivors of the disease have received rabies vaccine before the onset of illness. The approach to management of the rabies normally should be palliative. In unusual circumstances, a decision may be made to use an aggressive approach to therapy for patients who present at an early stage of clinical disease. No single therapeutic agent is likely to be effective, but a combination of specific therapies could be considered, including rabies vaccine, rabies immunoglobulin, monoclonal antibodies, ribavirin, interferon-alpha, and ketamine. Corticosteroids should not be used. As research advances, new agents may become available in the future for the treatment of human rabies.

PMID: 12491203, UI: 22378470

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Infect Immun 2003 Jan;71(1):575-9
 

Enhanced immunogenicity to Mycobacterium tuberculosis by vaccination with an alphavirus plasmid replicon expressing antigen 85A.

Kirman JR, Turon T, Su H, Li A, Kraus C, Polo JM, Belisle J, Morris S, Seder RA

Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Food and Drug Administration, Bethesda, Maryland 20892, USA.

[Medline record in process]
 

The immunogenicity of a plasmid DNA vaccine incorporating Sindbis virus RNA replicase functions (pSINCP) and expressing antigen 85A (Ag85A) from Mycobacterium tuberculosis was compared with a conventional plasmid DNA vector encoding Ag85A. pSINCP-85A was highly immunogenic in mice and gave enhanced long-term protection against M. tuberculosis compared with the conventional vector.

PMID: 12496215, UI: 22384187

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Infect Immun 2003 Jan;71(1):562-6
 

Feasibility of an HA2 Domain-Based Periodontitis Vaccine.

DeCarlo AA, Huang Y, Collyer CA, Langley DB, Katz J

Vaccine Research Division, Agenta Biotechnologies, Birmingham, Alabama 35253. Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294. Department of Biochemistry, University of Sydney, New South Wales 2006, Australia.

[Medline record in process]
 

In a rat periodontitis model, preinoculation with the Porphyromonas gingivalis HA2 binding domain for hemoglobin provided protection from disease. Protection was associated with induced anti-HA2 immunoglobulin G (IgG) humoral antibodies. The IgG subclass ratios suggested that relatively lower Th2/Th1-driven responses were directly associated with protection when rHA2 was administered in saline.

PMID: 12496212, UI: 22384184

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Infect Immun 2003 Jan;71(1):401-10
 

Intradermal infection model for pathogenesis and vaccine studies of murine visceral leishmaniasis.

Ahmed S, Colmenares M, Soong L, Goldsmith-Pestana K, Munstermann L, Molina R, McMahon-Pratt D

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.

[Medline record in process]
 

The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated with a pattern of parasite clearance with time postinfection in the liver and skin; in contrast, parasite persistence and expansion was observed in lymphoid tissue (spleen and draining lymph node). The course of disease found appears to be similar to those reported for subclinical canine and human visceral leishmaniasis. Clearance of parasites from the skin was correlated with an inflammatory response and the infiltration and activation of CD4(+) and CD8(+) T cells. In contrast, in lymphoid tissue (lymph node or spleen), the production of Th1/Th2 cytokines (interleukin-4 [IL-4], IL-10, and gamma interferon) appeared to correlate with parasite burden and pathogenesis. In vaccination experiments employing the Leishmania infantum D-13 (p80) antigen, significantly higher levels of protection were found with the intradermal murine model (29 to 7,500-fold more than naive controls) than were found with a low-dose intravenous infection model (9 to 173-fold). Thus, this model should prove useful for further investigation of disease pathogenesis as well as vaccine studies of visceral leishmaniasis.

PMID: 12496190, UI: 22384162

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Infect Immun 2003 Jan;71(1):374-83
 

Effective Protective Immunity to Yersinia pestis Infection Conferred by DNA Vaccine Coding for Derivatives of the F1 Capsular Antigen.

Grosfeld H, Cohen S, Bino T, Flashner Y, Ber R, Mamroud E, Kronman C, Shafferman A, Velan B

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.

[Medline record in process]
 

Three plasmids expressing derivatives of the Yersinia pestis capsular F1 antigen were evaluated for their potential as DNA vaccines. These included plasmids expressing the full-length F1, F1 devoid of its putative signal peptide (deF1), and F1 fused to the signal-bearing E3 polypeptide of Semliki Forest virus (E3/F1). Expression of these derivatives in transfected HEK293 cells revealed that deF1 is expressed in the cytosol, E3/F1 is targeted to the secretory cisternae, and the nonmodified F1 is rapidly eliminated from the cell. Intramuscular vaccination of mice with these plasmids revealed that the vector expressing deF1 was the most effective in eliciting anti-F1 antibodies. This response was not limited to specific mouse strains or to the mode of DNA administration, though gene gun-mediated vaccination was by far more effective than intramuscular needle injection. Vaccination of mice with deF1 DNA conferred protection against subcutaneous infection with the virulent Y. pestis Kimberley53 strain, even at challenge amounts as high as 4,000 50% lethal doses. Antibodies appear to play a major role in mediating this protection, as demonstrated by passive transfer of anti-deF1 DNA antiserum. Taken together, these observations indicate that a tailored genetic vaccine based on a bacterial protein can be used to confer protection against plague in mice without resorting to regimens involving the use of purified proteins.

PMID: 12496187, UI: 22384159

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Infect Immun 2003 Jan;71(1):354-64
 

Differential expression of gamma interferon mRNA induced by attenuated and virulent Mycobacterium tuberculosis in guinea pig cells after Mycobacterium bovis BCG vaccination.

Jeevan A, Yoshimura T, Lee KE, McMurray DN

Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Texas 77843, USA. ajeevan@medicine.tamu.edu

[Medline record in process]
 

To determine whether Mycobacterium bovis BCG vaccination would alter gamma interferon (IFN-gamma) mRNA expression in guinea pig cells exposed to Mycobacterium tuberculosis, we cloned a cDNA encoding guinea pig IFN-gamma from a spleen cell cDNA library. The cDNA is composed of 1,110 bp, with an open reading frame encoding a 166-amino-acid protein which shows 56 and 41% amino acid sequence homology to human and mouse IFN-gamma, respectively. Spleen or lymph node cells from naive and BCG-vaccinated guinea pigs were stimulated with purified protein derivative (PPD) or M. tuberculosis H37Ra or H37Rv, and the total RNA was subjected to Northern blot analysis with a (32)P-labeled probe derived from the cDNA clone. Compared to the IFN-gamma mRNA expression in cells of naive animals, that in spleen and lymph node cells exposed to various stimuli was enhanced after BCG vaccination. However, there was a significant reduction in IFN-gamma mRNA levels when cells were stimulated with a multiplicity of infection of greater than 1 virulent M. tuberculosis bacterium per 10 cells. The enhanced IFN-gamma mRNA response in BCG-vaccinated animals was associated with an increase in the proportions of CD4(+) T cells in the spleens, as determined by fluorescence-activated cell sorter analysis. Furthermore, the nonadherent population in the spleens enriched either by panning with anti-guinea pig immunoglobulin G-coated plates or by purification on nylon wool columns produced more IFN-gamma mRNA than whole spleen cells following stimulation with concanavalin A or PPD. This indicates that T cells are principally responsible for the upregulation of IFN-gamma mRNA expression following BCG vaccination. The mechanism by which virulent mycobacteria suppress IFN-gamma mRNA accumulation is currently under investigation.

PMID: 12496185, UI: 22384157

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Infect Immun 2003 Jan;71(1):309-16
 

A GRA1 DNA Vaccine Primes Cytolytic CD8(+) T Cells To Control Acute Toxoplasma gondii Infection.

Scorza T, D'Souza S, Laloup M, Dewit J, De Braekeleer J, Verschueren H, Vercammen M, Huygen K, Jongert E

Department of Toxoplasmosis, Pasteur Institute of Brussels, 1180 Brussels, Belgium.

[Medline record in process]
 

Protective immunity against Toxoplasma gondii is known to be mediated mainly by T lymphocytes and gamma interferon (IFN-gamma). The contribution of CD4(+) and CD8(+) T-lymphocyte subsets to protective immune responses against T. gondii infection, triggered by a GRA1 (p24) DNA vaccine, was assessed in this study. In vitro T-cell depletion experiments indicated that both CD4(+) and CD8(+) T-cell subsets produced IFN-gamma upon restimulation with a T. gondii lysate. In addition, the GRA1 DNA vaccine elicited CD8(+) T cells that were shown to have cytolytic activity against parasite-infected target cells and a GRA1-transfected cell line. C3H mice immunized with the GRA1 DNA vaccine showed 75 to 100% protection, while 0 to 25% of the mice immunized with the empty control vector survived challenge with T. gondii cysts. In vivo T-cell depletion experiments indicated that CD8(+) T cells were essential for the survival of GRA1-vaccinated C3H mice during the acute phase of T. gondii infection, while depletion of CD4(+) T cells led to an increase in brain cyst burden during the chronic phase of infection.

PMID: 12496180, UI: 22384152

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Infect Immun 2003 Jan;71(1):287-97
 

Impact of vector priming on the immunogenicity of recombinant salmonella vaccines.

Vindurampulle CJ, Attridge SR

Department of Molecular Biosciences, The University of Adelaide, Adelaide, South Australia 5005, Australia.

[Medline record in process]
 

There are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of experimental protocols identified two variables which might account for this inconsistency: the potential of the vector strain to colonize the murine gut-associated lymphoid tissue (GALT) and the nature of the foreign antigen subsequently delivered by the recombinant Salmonella construct. The former was investigated by constructing an aroA mutant of the Salmonella enterica serovar Stanley vector previously used in our laboratory. Although the introduction of an aroA mutation had surprisingly little effect on GALT colonization, it did reduce the strength of antilipopolysaccharide (anti-LPS) antibody responses and the impact of vector priming. Studies were also performed to ascertain the extent to which any observed hyporesponsiveness consequent upon vector priming might be determined by the characteristics of the foreign antigen. S. enterica serovar Stanley was used to deliver either of two Escherichia coli antigens, K88 pilus protein or the LT-B toxin subunit, to vector-primed mice. Both serum immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely abolished, and those to LT-B were significantly reduced, as a consequence of vector priming. When similar experiments were performed with an aroA S. enterica serovar Dublin vector, responses to K88 were significantly reduced but those to LT-B were unaffected by vector priming. Paradoxically, a priming infection with this vector induced stronger anti-LPS antibody responses but was less likely to elicit a state of hyporesponsiveness to subsequently presented foreign antigen. The impact of vector priming thus depends on both the Salmonella strain used and the nature of the foreign antigen, but our present data strengthen concerns that preexisting antivector immunity represents a serious threat to the Salmonella-based vaccine strategy.

PMID: 12496178, UI: 22384150

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Infect Immun 2003 Jan;71(1):275-86
 

Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine.

Harris SL, King WJ, Ferris W, Granoff DM

Children's Hospital Oakland Research Institute, Oakland, California. Department of Pediatrics, Children's Hospital Eastern Ontario, University of Ottawa, Ottawa, Canada.

[Medline record in process]
 

Serum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain of Neisseria meningitidis group C and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with approximately 10(3) CFU of either strain developed >5 x 10(5) CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 micro g/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 micro g/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.

PMID: 12496177, UI: 22384149

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Infect Immun 2003 Jan;71(1):109-16
 

Generation of Helicobacter pylori ghosts by PhiX protein E-mediated inactivation and their evaluation as vaccine candidates.

Panthel K, Jechlinger W, Matis A, Rohde M, Szostak M, Lubitz W, Haas R

Max von Pettenkofer Institute for Hygiene and Medical Microbiology, LMU Munich, Germany.

[Medline record in process]
 

Bacterial ghosts are empty cell envelopes, which may be generated by the controlled expression of the PhiX174 lysis gene E in gram-negative bacteria to obtain vaccine candidates. We describe here the application of this technology to Helicobacter pylori. The lysis gene cassette was cloned into an Escherichia coli-Helicobacter pylori shuttle vector and introduced into an H. pylori recipient strain by bacterial conjugation. Temperature induction of the lysis gene cassette revealed a quantitative killing of the H. pylori culture without induction of lysis-resistant bacteria. Biochemical and transmission electron microscopic studies identified structurally intact H. pylori. Prophylactic oral vaccination experiments using these H. pylori ghosts in the BALB/c mouse model showed a significant reduction of the bacterial load in the ghost group, as measured by a quantitative bacterial reisolation procedure. Ten of 10 and 5 of 10 mice were protected, respectively, without the use of a mucosal adjuvant. Coadministration of ghosts with cholera toxin as mucosal adjuvant resulted in a complete protection of 10 of 10 and 8 of 8 mice against H. pylori challenge, with three animals showing a sterile immunity.

PMID: 12496155, UI: 22384127

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J Immunol 2003 Jan 1;170(1):495-502
 

HIV mucosal vaccine: nasal immunization with gp160-encapsulated hemagglutinating virus of Japan-liposome induces antigen-specific CTLs and neutralizing antibody responses.

Sakaue G, Hiroi T, Nakagawa Y, Someya K, Iwatani K, Sawa Y, Takahashi H, Honda M, Kunisawa J, Kiyono H

Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

[Medline record in process]
 

Nasal immunization of normal mice with HIVgp160-encapsulated hemagglutinating virus of Japan (HVJ)-liposome induced high titers of gp160-specific neutralizing IgG in serum and IgA in nasal wash, saliva, fecal extract, and vaginal wash, along with both Th1- and Th2-type responses. HIVgp160-specific IgG- and IgA-producing cells were also detected in mononuclear cells isolated from spleen, nasal cavity, salivary gland, intestinal lamina propria, and vaginal tissue of nasally immunized mice. In addition, CD8(+) CTLs were induced in mice nasally immunized with gp160-HVJ-liposome. These findings suggest that two layers of effective HIV-specific humoral and cellular immunity, in mucosal and systemic sites, were induced by this nasal vaccine. In immunodeficient mice, nasal immunization with gp160-HVJ-liposome induced Ag-specific immune responses for the systemic and mucosal compartments of both Th1 (IFN-gamma(-/-)) and Th2 (IL-4(-/-)). In vitro Ag-specific serum IgG Ab and vaginal wash samples possessing IgA and IgG Abs that had been induced by nasal immunization with gp160-HVJ-liposome were able to neutralize a clinically isolated strain of HIV-MN strain isolated from Japanese hemophiliac patients. Taken together, these results suggest that, for the prevention and control of AIDS, nasally administered gp160-HVJ-liposome is a powerful immunization tool that induces necessary Ag-specific immune responses at different stages of HIV infection.

PMID: 12496436, UI: 22384509

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J Immunol 2003 Jan 1;170(1):99-106
 

OX40 Ligand-Transduced Tumor Cell Vaccine Synergizes with GM-CSF and Requires CD40-Apc Signaling to Boost the Host T Cell Antitumor Response.

Gri G, Gallo E, Di Carlo E, Musiani P, Colombo MP

Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. Department of Oncology and Neuroscience, G. D'Annunzio University of Chieti, Chieti, Italy.

[Medline record in process]
 

Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting. To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or together with GM-CSF (C26/GM/OX40L), which is known to activate APC. Mice injected with C26/OX40L cells displayed only a delay in tumor growth, while the C26/GM/OX40L tumor regressed in 85% of mice. Tumor rejection required granulocytes, CD4(+), CD8(+) T cells, and APC-mediated CD40-CD40 ligand cosignaling, but not IFN-gamma or IL-12 as shown using subset-depleted and knockout (KO) mice. CD40KO mice primed with C26/GM/OX40L cells failed to mount a CTL response, and T cells infiltrating the C26/GM/OX40L tumor were OX40 negative, suggesting an impairment in APC-T cell cross-talk in CD40KO mice. Indeed, CD4(+) T cell-depleted mice failed to mount any CTL activity against the C26 tumor, while treatment with agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4(+) T cells and restored CTL activation. C26/GM/OX40L cells cured 83% of mice bearing lung metastases, whereas C26/OX40L or C26/GM vaccination cured only 28 and 16% of mice, respectively. These results indicate the synergistic activity of OX40L and GM-CSF in a therapeutic setting.

PMID: 12496388, UI: 22384461

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J Immunol 2003 Jan 1;170(1):24-7
 

Cutting edge: dissociation between autoimmune response and clinical disease after vaccination with dendritic cells.

Bondanza A, Zimmermann VS, Dell'Antonio G, Dal Cin E, Capobianco A, Sabbadini MG, Manfredi AA, Rovere-Querini P

Cancer Immunotherapy and Gene Therapy Program, Clinical Immunology and Rheumatology Unit, and Division of Pathology, H. San Raffaele Scientific Institute, and Universita Vita-Salute San Raffaele, Milan, Italy.

[Medline record in process]
 

Autoimmunity represents a caveat to the use of dendritic cells (DCs) as adjuvant for human vaccines. We derived DCs from normal BALB/c mice or from mice prone to autoimmunity (NZB x NZW) F(1). We allowed DCs to phagocytose apoptotic thymocytes and vaccinated syngeneic animals. All mice developed anti-nuclear and anti-dsDNA Abs. Autoantibodies in normal mice were transient, without clinical or histological features of autoimmunity or tissue involvement. In contrast, autoimmunity was maintained in susceptible mice, which underwent renal failure and precociously died. The data suggest that DC vaccination consistently triggers autoimmune responses. However, clinical autoimmunity develops in susceptible subjects only.

PMID: 12496378, UI: 22384451

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J Infect Dis 2003 Jan 1;187(1):134-8
 

Long-term immunogenicity and efficacy of universal hepatitis B virus vaccination in taiwan.

Lin YC, Chang MH, Ni YH, Hsu HY, Chen DS

Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan.

[Medline record in process]
 

The long-term immunogenicity of universal hepatitis B virus (HBV) vaccine is seldom studied in large-scale prospective community-based populations, especially in adolescents. This study enrolled 1200 children aged 7 years with complete HBV immunization in infancy and determined HBV surface antigen (HBsAg), its antibody (anti-HBs), and HBV core antibody (anti-HBc) annually until the children were aged 14 years. Eleven children had new HBV infections with anti-HBc positivity as the only marker. None became positive for HBsAg or had detectable HBV DNA by polymerase chain reaction. The percentage of protective anti-HBs in 951 children without booster vaccination gradually decreased from 71.1% at age 7 years to 37.4% at age 12 years. Only 1 of the 200 children in the booster group and 2 of the 258 children in the nonbooster group developed new anti-HBc positivity. The results suggest that routine booster vaccination may not be required to provide protection against chronic HBV infection before age 15 years.

PMID: 12508157, UI: 22396208

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J Infect Dis 2002 Dec 1;186(11):1608-14
 

Spread of Streptococcus pneumoniae and antibiotic-resistant S. pneumoniae from day-care center attendees to their younger siblings.

Givon-Lavi N, Fraser D, Porat N, Dagan R

Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

A prospective study was conducted to determine the association between pneumococcal carriage among 36 infants and young toddlers cared for at home and carriage among their older siblings who attended 8 day-care centers (DCCs); 71 pneumococcal strains acquired by the younger siblings were compared with those present in the DCCs for 6 months. In 76% of cases, > or =1 strain identical by serotype and antibiogram was isolated in the older siblings' DCC versus 32%-63% in all other DCCs (P<.001). When phenotypically identical strains were compared by pulsed-field gel electrophoresis, the similarity between strains from older siblings' DCCs and the younger siblings' isolates was striking. This was not found when isolates from other DCCs were compared. Vaccinating DCC attendees with a 7-valent pneumococcal conjugate vaccine may play a key role in controlling the spread of antibiotic-resistant pneumococci, because the most resistant serotypes are included in the vaccine.

Publication Types:
 

• Clinical trial
• Randomized controlled trial

PMID: 12447737, UI: 22336647

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J Infect Dis 2002 Dec 1;186(11):1597-602
 

Neutralizing antibody induced in mice by novel glycoconjugates of human immunodeficiency virus type 1 gp120 and env2-3.

Paoletti LC, Kennedy RC

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. lpaoletti@channing.harvard.edu

We sought to determine whether conjugation methods could improve the immunogenicity of human immunodeficiency virus (HIV)-1 gp120 and env2-3, a nonglycosylated form of gp120. Conjugate vaccines were created by coupling tetanus toxoid (TT), gp120, and/or env2-3 with group B streptococcal type III polysaccharide (III) by reductive amination. Size-exclusion chromatography revealed polymers larger than those of the uncoupled proteins after conjugation. Geometric mean titers of gp120-specific immunoglobulin G (IgG) in serum from mice given env2-3-TT-III or env2-3-gp120-TT-III conjugates increased from <50 before to 3031 and 4756, respectively, after vaccination, whereas an uncoupled mixture of gp120, TT, and III, and III-TT not coupled with gp120 or env2-3 were poorly immunogenic. Pooled serum diluted 1rcolon;20 from mice given env2-3-gp120-TT-III inhibited infection of HIV-1(MN) of Sup-T1 cells and demonstrated neutralizing activity against infection with primary isolate HIV-1(BR014). HIV-1 gp120-specific IgG with neutralizing activity against HIV-1 can be induced with conjugates containing gp120, env2-3, III, and TT.

PMID: 12447735, UI: 22336645

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J Virol 2003 Jan;77(2):1653-7
 

A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3' untranslated region is highly attenuated and immunogenic in monkeys.

Whitehead SS, Falgout B, Hanley KA, Blaney Jr JE Jr, Markoff L, Murphy BR

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. swhitehead@niaid.nih.gov

[Medline record in process]
 

The Delta30 deletion mutation, which was originally created in dengue virus type 4 (DEN4) by the removal of nucleotides 172 to 143 from the 3' untranslated region (3' UTR), was introduced into a homologous region of wild-type (wt) dengue virus type 1 (DEN1). The resulting virus, rDEN1Delta30, was attenuated in rhesus monkeys to a level similar to that of the rDEN4Delta30 vaccine candidate. rDEN1Delta30 was more attenuated in rhesus monkeys than the previously described vaccine candidate, rDEN1mutF, which also contains mutations in the 3' UTR, and both vaccines were highly protective against challenge with wt DEN1. Both rDEN1Delta30 and rDEN1mutF were also attenuated in HuH-7-SCID mice. However, neither rDEN1Delta30 nor rDEN1mutF showed restricted replication following intrathoracic inoculation in the mosquito Toxorhynchites splendens. The ability of the Delta30 mutation to attenuate both DEN1 and DEN4 viruses suggests that a tetravalent DEN vaccine could be generated by introduction of the Delta30 mutation into wt DEN viruses belonging to each of the four serotypes.

PMID: 12502885, UI: 22391197

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J Virol 2003 Jan;77(2):1571-7
 

Development of a Dual Recombinant Vaccine To Protect Small Ruminants against Peste-des-Petits-Ruminants Virus and Capripoxvirus Infections.

Berhe G, Minet C, Le Goff C, Barrett T, Ngangnou A, Grillet C, Libeau G, Fleming M, Black DN, Diallo A

Cirad, Programme Sante Animale, Campus International de Baillarguet, 34398 Montpellier Cedex 05, France. Institute of Animal Health, Pirbright Laboratory, Pirbright, Surrey GU 24 ONF, United Kingdom. LANAVET, Garoua, Cameroon.

[Medline record in process]
 

A recombinant capripoxvirus vaccine containing a cDNA of the peste-des-petits-ruminants virus (PPRV) fusion protein gene was constructed. A quick and efficient method was used to select a highly purified recombinant virus clone. A trial showed that a dose of this recombinant as low as 0.1 PFU protected goats against challenge with a virulent PPRV strain.

PMID: 12502870, UI: 22391182

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J Virol 2003 Jan;77(2):1564-70
 

Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells.

Andrieu M, Desoutter JF, Loing E, Gaston J, Hanau D, Guillet JG, Hosmalin A

Departement d'Immunologie, Unite INSERM 567, UMR CNRS 8104, IFR 116, Institut Cochin, Paris. SEDAC-Therapeutics, Lille. EPI 99-08, Etablissement Francais du Sang-Alsace, Strasbourg, France.

[Medline record in process]
 

An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol(461-484)) and another lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8(+) T lymphocytes.

PMID: 12502869, UI: 22391181

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J Virol 2003 Jan;77(2):1163-74
 

Control of viremia and prevention of simian-human immunodeficiency virus-induced disease in rhesus macaques immunized with recombinant vaccinia viruses plus inactivated simian immunodeficiency virus and human immunodeficiency virus type 1 particles.

Willey RL, Byrum R, Piatak M, Kim YB, Cho MW, Rossio Jr JL Jr, Bess Jr J Jr, Igarashi T, Endo Y, Arthur LO, Lifson JD, Martin MA

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

[Medline record in process]
 

An effective vaccine against the human immunodeficiency virus type 1 (HIV-1) will very likely have to elicit both cellular and humoral immune responses to control HIV-1 strains of diverse geographic and genetic origins. We have utilized a pathogenic chimeric simian-human immunodeficiency virus (SHIV) rhesus macaque animal model system to evaluate the protective efficacy of a vaccine regimen that uses recombinant vaccinia viruses expressing simian immunodeficiency virus (SIV) and HIV-1 structural proteins in combination with intact inactivated SIV and HIV-1 particles. Following virus challenge, control animals experienced a rapid and complete loss of CD4(+) T cells, sustained high viral loads, and developed clinical disease by 17 to 21 weeks. Although all of the vaccinated monkeys became infected, they displayed reduced postpeak viremia, had no significant loss of CD4(+) T cells, and have remained healthy for more than 15 months postinfection. CD8(+) T-cell and neutralizing antibody responses in vaccinated animals following challenge were demonstrable. Despite the control of disease, virus was readily isolated from the circulating peripheral blood mononuclear cells of all vaccinees at 22 weeks postchallenge, indicating that immunologic control was incomplete. Virus recovered from the animal with the lowest postchallenge viremia generated high virus loads and an irreversible loss of CD4(+) T-cell loss following its inoculation into a naive animal. These results indicate that despite the protection from SHIV-induced disease, the vaccinated animals still harbored replication-competent and pathogenic virus.

PMID: 12502833, UI: 22391145

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J Virol 2003 Jan;77(2):1105-11
 

Identification and characterization of avian retroviruses in chicken embryo-derived yellow Fever vaccines: investigation of transmission to vaccine recipients.

Hussain AI, Johnson JA, Da Silva Freire M, Heneine W

HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia 30333. Fundacao Oswaldo Cruz/Bio-Manguinhos, Rio de Janeiro, Brazil 21045-900.

[Medline record in process]
 

All currently licensed yellow fever (YF) vaccines are propagated in chicken embryos. Recent studies of chick cell-derived measles and mumps vaccines show evidence of two types of retrovirus particles, the endogenous avian retrovirus (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the chicken embryonic fibroblast substrates. In this study, we investigated substrate-derived avian retrovirus contamination in YF vaccines currently produced by three manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF-FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT) activity was not possible because of assay inhibition. However, Western blot analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT proteins in all vaccines, indicating that more than one source is responsible for the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and particle-associated RNA from the YF vaccines showed no evidence of the long terminal repeat sequences of exogenous ALV subgroups A to D in any of the vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF-FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the vaccine-associated chicken substrate DNA was positive both for the nondefective ev-12 locus in two vaccines and for the defective ev-1 locus in all three vaccines. Both intact and ev-1 pol sequences were also identified in the particle-associated RNA. To investigate the risks of transmission, serum samples from 43 YF vaccine recipients were studied. None of the samples were seropositive by an ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT-PCR. YF vaccines produced by the three manufacturers all have particles containing EAV genomes and various levels of defective or nondefective ALV-E sequences. The absence of evidence of infection with ALV-E or EAV in 43 YF vaccine recipients suggests low risks for transmission of these viruses, further supporting the safety of these vaccines.

PMID: 12502826, UI: 22391138

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J Virol 2003 Jan;77(2):1049-58
 

Prevention of disease induced by a partially heterologous AIDS virus in rhesus monkeys by using an adjuvanted multicomponent protein vaccine.

Voss G, Manson K, Montefiori D, Watkins DI, Heeney J, Wyand M, Cohen J, Bruck C

GlaxoSmithKline Biologicals, Rixensart, Belgium. gerald.voss@gskbio.com

[Medline record in process]
 

Recombinant protein subunit AIDS vaccines have been based predominantly on the virus envelope protein. Such vaccines elicit neutralizing antibody responses that can provide type-specific sterilizing immunity, but in most cases do not confer protection against divergent viruses. In this report we demonstrate that a multiantigen subunit protein vaccine was able to prevent the development of disease induced in rhesus monkeys by a partially heterologous AIDS virus. The vaccine was composed of recombinant human immunodeficiency virus type 1 (HIV-1) gp120, NefTat fusion protein, and simian immunodeficiency virus (SIV) Nef formulated in the clinically tested adjuvant AS02A. Upon challenge of genetically unselected rhesus monkeys with the highly pathogenic and partially heterologous SIV/HIV strain SHIV(89.6p) the vaccine was able to reduce virus load and protect the animals from a decline in CD4-positive cells. Furthermore, vaccination prevented the development of AIDS for more than 2.5 years. The combination of the regulatory proteins Nef and Tat together with the structural protein gp120 was required for vaccine efficacy.

PMID: 12502820, UI: 22391132

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JAMA 2002 Dec 25;288(24):3155-8
 

Current controversies in vaccination: vaccine safety.

Maldonado YA

Department of Pediatrics, MC 5208, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305, USA. bonniem@stanford.edu

PMID: 12495396, UI: 22384596

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MMWR Morb Mortal Wkly Rep 2002 Nov 29;51(47):1070-2
 

Progress toward poliomyelitis eradication--Ethiopia, Somalia, and Sudan, January 2001-October 2002.

Since the World Health Assembly resolved in May 1988 to eradicate poliomyelitis, the estimated number of polio cases globally has declined >99%. The number of countries in which polio was estimated to be endemic decreased from 125 in 1988 to 10 in 2001, and three World Health Organization (WHO) regions (American, European, and Western Pacific) comprising approximately 55% of the world's population have been certified polio-free. Ethiopia, Somalia, and Sudan have achieved the lowest levels of poliovirus circulation since the polio eradication initiative began and are approaching interruption of transmission. This report describes intensified polio eradication activities in these countries during January 2001-October 2002, summarizes progress made, and highlights remaining challenges. Continued political commitment and financial support will be required to eradicate polio in these countries.

PMID: 12500908, UI: 22388684

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N Engl J Med 2002 Dec 26;347(26):2159-62
 

The global implications of influenza in Hong Kong.

Griffin MR, Neuzil KM

Publication Types:
 

• Comment
• Editorial
• Historical article

PMID: 12501229, UI: 22389630

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N Engl J Med 2002 Dec 19;
 

A Different View of Smallpox and Vaccination.

Mack T

[Record supplied by publisher]
 

Notice: To help to inform the current national debate about smallpox vaccination, this article has been published early (on December 19, 2002). The article will appear in the January 30, 2003, issue of the Journal. Click on "PDF of this article" for the full text. Copyright 2002 Massachusetts Medical Society

PMID: 12496354

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N Engl J Med 2002 Dec 19;
 

A Model for a Smallpox-Vaccination Policy.

Bozzette SA, Boer R, Bhatnagar V, Brower JL, Keeler EB, Morton SC, Stoto MA

[Record supplied by publisher]
 

Background The new reality of biologic terrorism and warfare has ignited a debate about whether to reintroduce smallpox vaccination. Methods We developed scenarios of smallpox attacks and built a stochastic model of outcomes under various control policies. We conducted a systematic literature review and estimated model parameters on the basis of European and North American outbreaks since World War II. We assessed the trade-offs between vaccine-related harms and benefits. Results Nations or terrorists possessing a smallpox weapon could feasibly mount attacks that vary with respect to tactical complexity and target size, and patterns of spread can be expected to vary according to whether index patients are hospitalized early. For acceptable results, vaccination of contacts must be accompanied by effective isolation. Vaccination of contacts plus isolation is expected to result in 7 deaths (from vaccine or smallpox) in a scenario involving the release of variola virus from a laboratory, 19 deaths in a human-vector scenario, 300 deaths in a building-attack scenario, 2735 deaths in a scenario involving a low-impact airport attack, and 54,728 deaths in a scenario involving a high-impact airport attack. Immediate vaccination of the public in an attacked region would provide little additional benefit. Prior vaccination of health care workers, who would be disproportionately affected, would save lives in large local or national attacks but would cause 25 deaths nationally. Prior vaccination of health care workers and the public would save lives in a national attack but would cause 482 deaths nationally. The expected net benefits of vaccination depend on the assessed probability of an attack. Prior vaccination of health care workers would be expected to save lives if the probability of a building attack exceeded 0.22 or if the probability of a high-impact airport attack exceeded 0.002. The probability would have to be much higher to make vaccination of the public life-saving. Conclusions The analysis favors prior vaccination of health care workers unless the likelihood of any attack is very low, but it favors vaccination of the public only if the likelihood of a national attack or of multiple attacks is high. Notice: To help to inform the current national debate about smallpox vaccination, this article has been published early (on December 19, 2002). The article will appear in the January 30, 2003, issue of the Journal. Click on "PDF of this article" for the full text. Click on "Supplementary Appendix 1" for a PDF file of supplementary text and tables. Copyright 2002 Massachusetts Medical Society

PMID: 12496353

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N Engl J Med 2002 Dec 19;
 

How Contagious Is Vaccinia?

Sepkowitz KA

[Record supplied by publisher]
 

Notice: To help to inform the current national debate about smallpox vaccination, this article has been published early (on December 19, 2002). The article will appear in the January 30, 2003, issue of the Journal. Click on "PDF of this article" for the full text. Copyright 2002 Massachusetts Medical Society

PMID: 12496351

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N Engl J Med 2002 Dec 19;
 

Smallpox Vaccination -- The Call to Arms.

Schraeder TL, Campion EW

[Record supplied by publisher]
 

Notice: To help to inform the current national debate about smallpox vaccination, this Perspective has been published early (on December 19, 2002). The article will appear in the January 30, 2003, issue of the Journal. Click on "PDF of this article" for the full text. Copyright 2002 Massachusetts Medical Society

PMID: 12496350

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Nat Med 2003 Jan;9(1):33-9
 

Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways.

Leitner WW, Hwang LN, DeVeer MJ, Zhou A, Silverman RH, Williams BR, Dubensky TW, Ying H, Restifo NP

National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

[Medline record in process]
 

Cancer vaccines targeting 'self' antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. Here, we describe a novel, naked DNA vaccine encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor antigen tyrosinase-related protein-1. Unlike conventional DNA vaccines, this vaccine can break tolerance and provide immunity to melanoma. The vaccine mediates production of double-stranded RNA, as evidenced by the autophosphorylation of dsRNA-dependent protein kinase R (PKR). Double-stranded RNA is critical to vaccine function because both the immunogenicity and the anti-tumor activity of the vaccine are blocked in mice deficient for the RNase L enzyme, a key component of the 2',5'-linked oligoadenylate synthetase antiviral pathway involved in double-stranded RNA recognition. This study shows for the first time that alphaviral replicon-encoding DNA vaccines activate innate immune pathways known to drive antiviral immune responses, and points the way to strategies for improving the efficacy of immunization with naked DNA.

PMID: 12496961, UI: 22402164

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Nat Med 2003 Jan;9(1):27-32
 

Therapeutic dendritic-cell vaccine for simian AIDS.

Lu W, Wu X, Lu Y, Guo W, Andrieu JM

Institut de Recherche sur les Vaccins et l'Immunotherapie des Cancers et du Sida, Paris, France.

[Medline record in process]
 

An effective immune response against human immunodeficiency virus or simian immunodeficiency virus (SIV) is critical in achieving control of viral replication. Here, we show in SIV-infected rhesus monkeys that an effective and durable SIV-specific cellular and humoral immunity is elicited by a vaccination with chemically inactivated SIV-pulsed dendritic cells. After three immunizations made at two-week intervals, the animals exhibited a 50-fold decrease of SIV DNA and a 1,000-fold decrease of SIV RNA in peripheral blood. Such reduced viral load levels were maintained over the remaining 34 weeks of the study. Molecular and cellular analyses of axillary and inguinal node lymphocytes of vaccinated monkeys revealed a correlation between decreased SIV DNA and RNA levels and increased SIV-specific T-cell responses. Neutralizing antibody responses were augmented and remained elevated. Inactivated whole virus-pulsed dendritic cell vaccines are promising means to control diseases caused by immuno- deficiency viruses.

PMID: 12496959, UI: 22402162

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Pediatrics 2002 Oct;110(4):820-3
 

Control of disease attributable to Haemophilus influenzae type b and the national immunization program.

Meissner HC, Pickering LK

Division of Pediatric Infectious Disease, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA. cmeissner@lifespan.org

Publication Types:
 

• Comment

PMID: 12359800, UI: 22247533

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Science 2002 Nov 29;298(5599):1730-1
 

Historical essay. Prospects for the future.

Gallo RC, Montagnier L

Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA.

PMID: 12459577, UI: 22347842

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Vaccine 2002 May 22;20(17-18):2396-403
 

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Liao HX, Cianciolo GJ, Staats HF, Scearce RM, Lapple DM, Stauffer SH, Thomasch JR, Pizzo SV, Montefiori DC, Hagen M, Eldridge J, Haynes BF

Department of Medicine, Duke Human Vaccine Institute, Duke University Medical Center, Box 3258, Durham, NC 27710, USA. hliao@duke.edu

Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen required for optimal immunogenicity. We have evaluated activated alpha2-macroglobulin (alpha2M*) and a squalene-based stable emulsion containing monophosphoryl lipid A (MPL-SE) with granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvants to enhance the immunogencity of candidate HIV immunogens. Balb/c mice were subcutaneously immunized on days 0, 14 and 28 with 100-0.1 microg of HIV-1 envelope gp120 C4-V3 immunogens from either HIV IIIB (C4-V3(IIIB)) or SHIV 89.6P (C4-V3(89.6P)). Immunogens were tested covalently coupled to alpha2M*, formulated with MPL-SE/GM-CSF, or as a combination of both. Using CFA/IFA, only 50 and 100 microg, but not lower doses of C4-V3(IIIB) peptides, induced antibody responses. In contrast, peak antibody responses were detected in mice immunized with 10 microg of C4-V3 peptide coupled to alpha2M* (alpha2M*-peptide). Similar to CFA/IFA, MPL-SE/GM-CSF induced optimal antibody responses at 50 and 100 microg of C4-V3 immunogen. However, the combination of MPL-SE/GM-CSF with alpha2M*-C4-V3 peptide decreased the dose of C4-V3 required for optimal response to 5 microg for C4-V3(IIIB), and to 0.1 microg for C4-V3(89.6P). Taken together, HIV envelope gp120 C4-V3 peptides covalently complexed with alpha2M* and formulated with MPL-SE/GM-CSF resulted in a subunit HIV immunogen capable of inducing anti-HIV envelope antibody responses at doses up to 100-fold less than those needed with CFA/IFA or MPL-SE/GM-CSF alone.

PMID: 12009296, UI: 22008465

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Vaccine 2002 May 22;20(17-18):2348-57
 

DNA immunization against the clumping factor A (ClfA) of Staphylococcus aureus.

Brouillette E, Lacasse P, Shkreta L, Belanger J, Grondin G, Diarra MS, Fournier S, Talbot BG

Departement de Biologie, Faculte des Sciences, Universite de Sherbrooke, Sherbrooke, Canada.

Adhesins are considered the most important virulence factors during early phases Staphylococcus aureus infection. Antibodies induced by vaccination toward an adhesin should reduce the adherence of the pathogen and augment its phagocytosis. The present report describes the immune response of mice to a DNA vaccine directed against one of these adhesins, clumping factor A (ClfA). Injection of plasmids expressing the fibrinogen-binding region A of ClfA induced a strong and specific antibody response to ClfA in mice. In addition, splenocyte proliferation was provoked by in vitro stimulation with recombinant ClfA, thus, indicating direct implication of these cells in the immune response. Pre-incubation of S. aureus with sera of vaccinated mice reduced the pathogen's ability to bind fibrinogen by up to 92%. These pre-incubated bacteria were phagocytosed by macrophages at an increased level in vitro and were less virulent in vivo in a mouse mastitis model. However, DNA-immunized mice were not protected against an intraperitoneal challenge. Overall, the results suggest that DNA immunization against adhesins represents a new and valuable approach to combat S. aureus infections.

PMID: 12009291, UI: 22008460

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Vaccine 2002 May 22;20(17-18):2278-86
 

Immunisation of dairy cattle with recombinant Streptococcus uberis GapC or a chimeric CAMP antigen confers protection against heterologous bacterial challenge.

Fontaine MC, Perez-Casal J, Song XM, Shelford J, Willson PJ, Potter AA

Veterinary Infectious Disease Organisation, University of Saskatchewan, Saskatoon, Canada.

The gapC genes, encoding the cell surface-associated GapC proteins of S. uberis and S. agalactiae, have been cloned and sequenced. To identify potential vaccine candidates against S. uberis-induced bovine mastitis, lactating dairy cows were vaccinated with either (6 x His)GapC of S. uberis or S. dysgalactiae, or with a chimeric CAMP-factor antigen, CAMP-3. For 7 days following heterologous challenge with S. uberis, milk somatic cell counts were determined to assess differences in the severity of mastitis between vaccinates and an unvaccinated control group. Vaccination with S. uberis (6 x His)GapC or CAMP-3 resulted in a significant reduction in inflammation on several days post-challenge, most significantly for the former antigen. Inflammation was not reduced in S. dysgalactiae (6 x His)GapC vaccinates, suggesting that it does not confer cross-species protection.

PMID: 12009283, UI: 22008452

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Vaccine 2002 May 22;20(17-18):2174-80
 

Streptococcus pneumoniae polysaccharides conjugated to the outer membrane protein A from Klebsiella pneumoniae elicit protective antibodies.

Libon C, Haeuw JF, Crouzet F, Mugnier C, Bonnefoy JY, Beck A, Corvaia N

Centre d'Immunologie Pierre Fabre, 5 Avenue Napoleon III, St. Julien en Genevois, France. christine.libon@pierre-fabre.com

Polysaccharides (PSs) derived from Streptococcus pneumoniae include more than 90 serotypes and differ greatly in their immunogenicity. In addition, immunization with PSs does not induce high affinity antibody production and no memory B-cells are generated. Coupling PSs to carrier proteins has been reported to induce B-cell maturation and to install a B-cell memory. As an alternative carrier protein, the outer membrane protein A (OmpA) derived from Klebsiella pneumoniae has been coupled to various PSs. We evaluated the immunogenicity of two PS conjugates, using PS derived from S. pneumoniae types 14 and 19. In this report, we show that anti-PS IgG responses are generated after the conjugation of PSs to P40. In addition, the humoral response generated is able to protect mice from a bacterial challenge. Our results indicate that P40 could be included in the development of new PS conjugate vaccines.

PMID: 12009270, UI: 22008439

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Vaccine 2002 May 22;20(17-18):2153-4
 

Flu in the limelight.

Rimmelzwaan CF, Osterhaus AD

Publication Types:
 

• Editorial

PMID: 12009266, UI: 22008435

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Wkly Epidemiol Rec 2002 Nov 22;77(47):394-404
 

Draft WHO guidelines on the use of vaccines and antivirals during influenza pandemics.

PMID: 12498024, UI: 22386561

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Wkly Epidemiol Rec 2002 Nov 22;77(47):389-94
 

Global Advisory Committee on Vaccine Safety, 20-21 June 2002.

PMID: 12498023, UI: 22386560

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