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Infect Immun 2002 Nov;70(11):6499-503
 

Multiparameter selection of Helicobacter pylori antigens identifies two novel antigens with high protective efficacy.

Sabarth N, Hurwitz R, Meyer TF, Bumann D

Department of Molecular Biology, Max-Planck-Institute for Infection Biology, D-10117 Berlin, Germany.

A multiparameter selection of Helicobacter pylori antigens for vaccine development identified 15 candidates, 6 of which are known protective antigens. Two novel antigens with low homology to other organisms (HP0231 and HP0410) were overexpressed and purified with high yields. Both confer protective immunity in the mouse Helicobacter infection model.

PMID: 12379737, UI: 22267155

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Infect Immun 2002 Nov;70(11):6494-8
 

A comparison of murine and human immunoproteomes of Helicobacter pylori validates the preclinical murine infection model for antigen screening.

Bumann D, Holland P, Siejak F, Koesling J, Sabarth N, Lamer S, Zimny-Arndt U, Jungblut PR, Meyer TF

Department of Molecular Biology, Max-Planck-Institute for Infection Biology, Berlin, Germany.

Preclinical mouse infection models are widely used for Helicobacter vaccine development, but how well such models mimic important aspects of human infections is unknown. A comparison of Helicobacter pylori immunoproteomes of infected mice with previously reported patient data reveals a high agreement in the antigens recognized, suggesting that H. pylori in vivo protein composition and recognition by the host immune system are comparable in mice and humans. Murine Helicobacter models may thus be valid to screen antigens for human vaccination.

PMID: 12379736, UI: 22267154

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Infect Immun 2002 Nov;70(11):6464-7
 

The N-terminal domain of RTX toxin ApxI of Actinobacillus pleuropneumoniae elicits protective immunity in mice.

Seah JN, Frey J, Kwang J

Laboratory of Animal Health Biotechnology, Temasek Life Sciences Laboratory, The National University of Singapore, Singapore 117604, Singapore.

We expressed three Actinobacillus pleuropneumoniae ApxI deletion derivatives to map the domain that could induce protective immunity. Antiserum to ApxI N-terminal covered by residues 40 to 380 was found to neutralize ApxI hemolytic activity but not ApxIII cytotoxicity. When used as a subunit vaccine in mice, this recombinant N-terminal fragment elicited protection against lethal infection with heterologous A. pleuropneumoniae serovars.

PMID: 12379729, UI: 22267147

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Infect Immun 2002 Nov;70(11):6231-41
 

Postexposure prophylaxis against anthrax: evaluation of various treatment regimens in intranasally infected guinea pigs.

Altboum Z, Gozes Y, Barnea A, Pass A, White M, Kobiler D

Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 74100, Israel. altboum@iibr.gov.il

The efficiency of postexposure prophylaxis against Bacillus anthracis infection was tested in guinea pigs infected intranasally with either Vollum or strain ATCC 6605 spores (75 times the 50% lethal dose [LD(50)] and 87 times LD(50,) respectively). Starting 24 h postinfection, animals were treated three times per day for 14 days with ciprofloxacin, tetracycline, erythromycin, cefazolin, and trimethoprim-sulfamethoxazole (TMP-SMX). Administration of cefazolin and TMP-SMX failed to protect the animals, while ciprofloxacin, tetracycline, and erythromycin prevented death. Upon cessation of treatment all erythromycin-treated animals died; of the tetracycline-treated animals, two of eight infected with Vollum and one of nine infected with ATCC 6605 survived; and of the ciprofloxacin group injected with either 10 or 20 mg/kg of body weight, five of nine and five of five animals, respectively, survived. To test the added value of extending the treatment period, Vollum-infected (46 times the LD(50)) animals were treated for 30 days with ciprofloxacin or tetracycline, resulting in protection of eight of nine and nine of nine animals, respectively. Once treatment was discontinued, only four of eight and five of nine animals, respectively, survived. Following rechallenge (intramuscularly) of the survivors with 30 times the LD(50) of Vollum spores, all ciprofloxacin-treated animals were protected while none of the tetracycline-treated animals survived. In an attempt to confer protective immunity lasting beyond the termination of antibiotic administration, Vollum-infected animals were immunized with a protective antigen (PA)-based vaccine concurrently with treatment with either ciprofloxacin or tetracycline. The combined treatment protected eight of eight and nine of nine animals. Following cessation of antibiotic administration seven of eight and eight of eight animals survived, of which six of seven and eight of eight resisted rechallenge. These results indicate that a combined treatment of antibiotics together with a PA-based vaccine could provide long-term protection to prevent reoccurrence of anthrax disease.

PMID: 12379702, UI: 22267120

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Infect Immun 2002 Nov;70(11):6021-31
 

Sequential immunization with vesicles prepared from heterologous Neisseria meningitidis strains elicits broadly protective serum antibodies to group B strains.

Moe GR, Zuno-Mitchell P, Hammond SN, Granoff DM

Children's Hospital Oakland Research Institute, Oakland, California 94609-1673, USA.

The capsular polysaccharide of Neisseria meningitidis group B is an autoantigen, whereas noncapsular antigens are highly variable. These factors present formidable challenges for development of a broadly protective and safe group B vaccine. Mice and guinea pigs were sequentially immunized with three doses of micovesicles or outer membrane vesicles prepared from three meningococcal strains that were each antigenically heterologous with respect to the two major porin proteins, PorA and PorB, and the group capsular polysaccharide. The resulting antisera conferred passive protection against meningococcal group B bacteremia in infant rats and elicited complement-mediated bactericidal activity against genetically diverse group B strains that were either homologous or heterologous with respect to PorA of the strains used to prepare the vaccine. By using knockout strains, a portion of the bactericidal antibody was directed against the highly conserved protein, neisserial surface protein A (NspA). Further, an anti-NspA monoclonal antibody elicited by the sequential immunization was highly bactericidal against strains that were previously shown to be resistant to bacteriolysis by anti-NspA antibodies produced by immunization with recombinant NspA. Sequential immunization with heterologous vesicle preparations offers a novel approach to eliciting broadly protective immunity against N. meningitidis strains. An NspA-based vaccine prepared from protein expressed by Neisseria also may be more effective than the corresponding recombinant protein made in Escherichia coli.

PMID: 12379678, UI: 22267096

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J Immunol 2002 Oct 15;169(8):4511-21
 

Differences between T cell epitopes recognized after immunization and after infection.

Vogel TU, Horton H, Fuller DH, Carter DK, Vielhuber K, O'Connor DH, Shipley T, Fuller J, Sutter G, Erfle V, Wilson N, Picker LJ, Watkins DI

Wisconsin National Primate Research Center, University of Wisconsin, 1220 Capital Court, Madison, WI 53715, USA.

Evidence suggests that cellular immune responses play a crucial role in the control of HIV and SIV replication in infected individuals. Several vaccine strategies have therefore targeted these CD8(+) and CD4(+) responses. Whether vaccination induces the same repertoire of responses seen after infection is, however, a key unanswered question in HIV vaccine development. We therefore compared the epitope specificity induced by vaccination to that present postchallenge in the peripheral blood. Intracellular cytokine staining of PBMC stimulated with overlapping 15/20-mer peptides spanning the proteins of SIV were measured after DNA/modified vaccinia Ankara vaccination of eight rhesus macaques. Lymphocytes from 8 animals recognized a total of 39 CD8 epitopes and 41 CD4 epitopes encoded by the vaccine. T cell responses were again monitored after challenge with SIVmac239 to investigate the evolution of these responses. Only 57% of all CD8(+) T cell responses and 19% of all CD4(+) T cell responses present after vaccination were recalled after infection as measured in the peripheral blood. Interestingly, 29 new CD8 epitopes and 5 new CD4 epitopes were recognized by PBMC in the acute phase. These new epitopes were not detected after vaccination, and only some of them were maintained in the chronic phase (33% of CD8 and no CD4 responses). Additionally, 24 new CD8 epitopes and 7 new CD4 epitopes were recognized by PBMC in the chronic phase of infection. The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection.

PMID: 12370388, UI: 22257697

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J Infect Dis 2002 Oct 15;186(8):1098-105
 

Mucosal immunization with inactivated human immunodeficiency virus plus CpG oligodeoxynucleotides induces genital immune responses and protection against intravaginal challenge.

Dumais N, Patrick A, Moss RB, Davis HL, Rosenthal KL

Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Centre, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.

Vaccines capable of protecting against sexually transmitted infections, such as human immunodeficiency virus (HIV), will depend on the induction of potent long-lasting mucosal immune responses in the genital tract. We evaluated vaginal and systemic immune responses and protection from vaginal challenge elicited after intranasal immunization of mice with inactivated glycoprotien 120-depleted HIV-1 immunogen alone or in combination with immunostimulatory CpG oligodeoxynucleotides (ODNs). Mice immunized with HIV-1 immunogen plus CpG ODN had significantly enhanced levels of anti-protein 24 immunoglobulin (Ig) G and IgA antibodies in serum and vaginal washes and increased production of beta-chemokines and interferon-gamma, compared with mice immunized with HIV-1 immunogen alone or with control ODN. Furthermore, mice intranasally immunized with HIV-1 immunogen plus CpG were protected against intravaginal challenge with a recombinant vaccinia virus expressing HIV-1 gag. These results indicate that mucosal immunization with whole-killed HIV-1 plus CpG ODN may be an effective means of inducing local immunity and protection against genital infection.

PMID: 12355360, UI: 22242171

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Lancet 2002 Oct 5;360(9339):1050-5
 

Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial.

Mwinga A, Nunn A, Ngwira B, Chintu C, Warndorff D, Fine P, Darbyshire J, Zumla A

University of Zambia-University College London Tuberculosis/HIV Research and Training Project, Lusaka, Zambia.

BACKGROUND: Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients. METHODS: The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result. FINDINGS: Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172. INTERPRETATION: Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated.

Publication Types:
 

• Clinical trial
• Multicenter study
• Randomized controlled trial

PMID: 12383985, UI: 22272082

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Lancet 2002 Oct 5;360(9339):1032-3
 

Whither Mycobacterium vaccae--encore.

Fourie PB, Ellner JJ, Johnson JL

Medical Research Council, Pretoria, South Africa. bernard.fourie@mrc.ac.za

Publication Types:
 

• Comment

PMID: 12383977, UI: 22272074

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Nat Med 2002 Oct;8(10):1171-4
 

A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis.

Sambandamurthy VK, Wang X, Chen B, Russell RG, Derrick S, Collins FM, Morris SL, Jacobs WR Jr

Howard Hughes Medical Institute and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.

With the advent of HIV and the widespread emergence of drug-resistant strains of Mycobacterium tuberculosis, newer control strategies in the form of a better vaccine could decrease the global incidence of tuberculosis. A desirable trait in an effective live attenuated vaccine strain is an ability to persist within the host in a limited fashion in order to produce important protective antigens in vivo. Attenuated M. tuberculosis vaccine candidates have been constructed by deleting genes required for growth in mice. These candidate vaccines did not elicit adequate protective immunity in animal models, due to their inability to persist sufficiently long within the host tissues. Here we report that an auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate auxotroph survived significantly longer (250 days) than mice infected with either bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35 days, respectively). Subcutaneous immunization with this auxotroph conferred protection in C57BL/6J mice against an aerosol challenge with virulent M. tuberculosis, which was comparable with that afforded by BCG vaccination. Our findings highlight the importance of de novo pantothenate biosynthesis in limiting the intracellular survival and pathogenesis of M. tuberculosis without reducing its immunogenicity in vaccinated mice.

PMID: 12219086, UI: 22244557

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Pediatr Infect Dis J 2002 Oct;21(10):931-5
 

Hospitalizations for varicella in the United States, 1988 to 1999.

Galil K, Brown C, Lin F, Seward J

Centers for Disease Control and Prevention, Atlanta, GA, USA.

BACKGROUND: Varicella epidemiology is changing with increasing use of the varicella vaccine. METHODS: To describe the epidemiology of severe varicella disease before and after vaccine introduction, data from the National Hospital Discharge Survey (NHDS) for 1988 to 1999 were analyzed. Incidental cases of varicella in persons hospitalized for a different indication were excluded. RESULTS: In the prevaccination era (1988 to 1995), there were 10 632 varicella hospitalizations annually. The most common complications were viral pneumonitis (20.9%), fluid/electrolyte disturbances (19.3%) and soft tissue infections (17.8%). Most (89.1%) persons had no severe underlying immunocompromising conditions. The mean length of hospitalization was 5.4 days, corresponding to approximately 57 000 days of hospitalization annually. In the first years after vaccine licensure (1996 to 1999), vaccine coverage reached 59%. Although not statistically significant, there was a trend toward decreased hospitalizations and a decline in mean length of hospitalization. CONCLUSIONS: Varicella morbidity was higher in the prevaccination era than previously reported. Although no significant decline is evident, a trend toward decreased hospitalizations is emerging in the first years after vaccine introduction.

PMID: 12394815, UI: 22282228

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Pediatr Infect Dis J 2002 May;21(5):446-8
 

The natural course of nonsuppurative Calmette-Guerin bacillus lymphadenitis.

Singla A, Singh S, Goraya JS, Radhika S, Sharma M

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

In a tertiary level hospital in North India, we studied the outcome of infants with nonsuppurative Calmette-Guerin bacillus (BCG) lymphadenitis managed conservatively. Twenty-three infants with nonsuppurative BCG lymphadenitis diagnosed on the basis of clinical presentation, evidence of granulomatous inflammation and demonstration of acid fast bacilli in the aspirated material were followed prospectively without being offered specific antitubercular drug therapy. Twenty patients were available for final analysis; three were lost to follow-up. Seventeen (85%) had spontaneous regression of BCG lymphadenitis without progression and drainage. The mean time to resolution was 9.1 months. Three (15%) patients developed suppuration and drainage, but even these children had uneventful healing on conservative management only. Nonsuppurative BCG lymphadenitis follows a benign course in most individuals. Most of the cases regress spontaneously with conservative management.

PMID: 12150189, UI: 22144732

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Science 2002 Oct 11;298(5592):351-3
 

Microbiology. Domino effects from battles against microbes.

Cohen J

Publication Types:
 

• Congresses
• News

PMID: 12376683, UI: 22264069

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Science 2002 Oct 11;298(5592):339
 

Bacterial meningitis. Appeal to thwart deadly outbreak.

Vogel G

Publication Types:
 

• News

PMID: 12376673, UI: 22264059

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Vaccine 2002 May 15;20 Suppl 2:S5-14
 

Influenza and the work of the World Health Organization.

Kitler ME, Gavinio P, Lavanchy D

World Health Organization (WHO), CH 1211 27, Geneva, Switzerland. kitlerm@who.ch

Before World War I, influenza was not considered a particularly serious problem. The great pandemic of 1918-1919 changed all that, and the possibility that such a catastrophe could occur again has conditioned all subsequent developments.In epidemiological terms, the hallmark of an influenza is the excess mortality that it causes combined with an enormous burden of ill-health that saps the energy of individuals, families and communities throughout the whole world. In order to engage in influenza prevention and control, the global influenza surveillance network was set up by World Health Organization (WHO) in 1948 as a worldwide alert system for the identification of new influenza viruses, gathering information from 110 participating laboratories in 82 countries and four WHO Collaborating Centers for Influenza reference and research: Centers for Disease Control and Prevention, Atlanta (USA), National Institute for Medical Research, London (UK), WHO Collaborating Centre for Influenza Reference and Research, Melbourne (Australia) and the National Institute for Infectious Diseases, Tokyo (Japan).This network helps WHO to monitor influenza activity all over the world and provides the organization with the viral isolates and information it requires to decide which new virus strains will be used to produce influenza vaccines during the following season. Each year, information about the isolates over the previous 12 months is analyzed and used to determine the composition of the influenza vaccine to be administered during the coming influenza season both for the northern and southern hemisphere. If necessary, the recommendations for the southern hemisphere differ from the ones formulated for the northern hemisphere vaccine. The information supplied by this network enables the organization to regularly update its World Wide Web (WWW) site (FluNet), which reports on the situation of diseases.This network will also enable the WHO to detect a new influenza pandemic as early as possible.

PMID: 12110248, UI: 22107880

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Vaccine 2002 Jun 7;20(19-20):2562-78
 

Economic evaluation of strategies for the control and management of influenza in Europe.

Scuffham PA, West PA

York Health Economics Consortium, University of York, York, UK. pas8@york.ac.uk

We compared the cost-effectiveness of different strategies for the control and management of influenza for the elderly populations in three European countries (England and Wales, France, Germany). A "no intervention" scenario was compared with six control strategies: opportunistic vaccination (passive recruitment), comprehensive vaccination programmes (active recruitment), 4 weeks chemoprophylaxis course using neuraminidase inhibitors (NIs), 4 weeks chemoprophylaxis course using ion-channel inhibitors (ICIs), early treatment with NIs, and early treatment with ICIs. Vaccination strategies were the most cost-effective. Chemoprophylaxis strategies were highly expensive even under assumptions of optimal timing. Early treatment strategies with antivirals substantially increased demand for GP services and were more expensive than prevention through vaccination.

PMID: 12057614, UI: 22053738

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Vaccine 2002 Jun 7;20(19-20):2551-5
 

Effects of adsorption of acellular pertussis antigens onto different aluminium salts on the protective activity in an intranasal murine model of Bordetella pertussis infection.

Denoel P, Poolman J, Carletti G, Veitch K

Research and Development, GlaxoSmithKline Biologicals, Rue de l'Institut 89, B-1330 Rixensart, Belgium.

Adsorption of the pertussis antigens, pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) onto aluminium phosphate rather than aluminium hydroxide leads to a lower humoral response and poorer protection against intranasal pertussis challenge in mice. These effects could be reversed by inclusion of fimbriae (FIM) 2 and 3 in the formulation. These data emphasis the importance of correct formulation for such vaccines.

PMID: 12057612, UI: 22053736

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Vaccine 2002 Jun 7;20(19-20):2537-45
 

Intranasal immunization with SIV virus-like particles (VLPs) elicits systemic and mucosal immunity.

Yao Q, Vuong V, Li M, Compans RW

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. qizhiyab@bcm.tmc.edu

By using a baculovirus expression system, we have successfully produced simian immunodeficiency virus (SIV)-like particles (VLPs) with high levels of biologically active SIV envelope (Env) incorporated on their surfaces. To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route. High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent. The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented. Mice immunized with VLPs plus CT were found to exhibit higher serum antibody responses than those immunized with VLPs alone (P<0.001). Furthermore, IgA antibody production was detected in both saliva and vaginal fluid from mice mucosally immunized with SIV VLPs. Higher levels of IgA were found in vaginal fluid than in saliva in animals immunized with SIV VLPs plus CT (P<0.05). Higher neutralizing activity to SIV 1A11 was also found in serum of animals immunized with SIV VLPs plus CT. Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT. These results suggest that VLPs are effective mucosal antigens that can induce both humoral and cellular immune responses at systemic and mucosal sites.

PMID: 12057610, UI: 22053734

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Vaccine 2002 Jun 7;20(19-20):2508-15
 

Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom.

Aggarwal N, Zhang Z, Cox S, Statham R, Alexandersen S, Kitching RP, Barnett PV

Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey, UK. neeraj.aggarwal@bbsrc.ac.uk

In 2001, the United Kingdom experienced its worst epidemic of foot-and-mouth disease (FMD). To date approximately 3.9 million animals have been culled and direct and indirect revenue losses are probably in excess of pound 12 billion. This study was carried out to investigate the biological characteristics of the FMD virus strain O/UKG/2001 responsible for the epidemic. Animal transmission experiments indicated that this strain is not host restricted and will infect the three main susceptible livestock species (cattle, sheep and pigs). Immunisation with high potency emergency vaccine derived from O(1) Manisa strain of FMD virus protected all three species against clinical disease when challenged with FMD virus strain O/UKG/2001.

PMID: 12057606, UI: 22053730

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Vaccine 2002 May 6;20(15):2011-5
 

The advantage of early recognition of HIV-infected cells by cytotoxic T-lymphocytes.

Gruters RA, van Baalen CA, Osterhaus AD

Department of Virology, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.

Accumulating evidence indicates that cytotoxic T-lymphocytes (CTL) play an important role in the clearing of primary and control of chronic human immunodeficiency virus (HIV) infection. Here, we discuss recent findings that indicate that the timing of target cell recognition critically contributes to CTL effectiveness. In this light several problems that have troubled CTL research are discussed. The use of early proteins like Tat and Rev is proposed for future vaccines design.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983265, UI: 21980826

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Vaccine 2002 May 6;20(15):1988-93
 

HIV subtypes and recombination strains--strategies for induction of immune responses in man.

Wahren B, Ljungberg K, Rollman E, Levi M, Zuber B, Kjerrstrom Zuber A, Hinkula J, Leandersson AC, Calarota S, Hejdeman B, Bratt G, Sandstrom E

Swedish Institute for Infectious Disease Control, Department of Venereology, South Hospital, Karolinska Institute, 171 82 Stockholm, Sweden. britta.wahren@smi.ki.se

Clinical and experimental studies of HIV-1 subcomponents were made in order to increase their immunogenicity. HIV subtype envelopes A, B and C have been compared and a detailed analysis made by peptides of the coreceptor-ligand interactions. We identified a direct interaction between HIV-1 envelope and a cellular receptor at the amino acid level. Both the viral subtype and its tropism appeared to influence inhibition of infection. Genetic immunization induced new cytotoxic responses while proteins appeared to efficiently boost previous responses. One HIV-1 subtype B antigen was strongly immunogenic in a human immunotherapeutic trial and permitted better survival at 2 years of the study in patients with poor prognosis.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983260, UI: 21980821

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Vaccine 2002 May 6;20(15):1985-7
 

Mechanisms of protection against simian immunodeficiency virus infection.

Johnson RP

Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772, USA. paul.johnson@hms.harvard.edu

One of the obstacles to the development of an effective AIDS vaccine has been the limited information on the mechanisms of protective immunity to HIV. In macaques, immunization with attenuated simian immunodeficiency viruses (SIV) has proved to be one of the most effective strategies to induce protection against infection or disease with pathogenic lentiviruses. Infection with attenuated SIV strains induces a broad range of SIV-specific immune responses, including relatively potent cytotoxic T lymphocyte (CTL) and antibody responses. Several studies of macaques vaccinated with attenuated SIV have demonstrated correlations between CTL responses or antibody responses and protection but more detailed studies are needed to document the relative importance of these responses in protective immunity.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983259, UI: 21980820

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Vaccine 2002 May 6;20(15):1968-74
 

Development of an oral prime-boost strategy to elicit broadly neutralizing antibodies against HIV-1.

Devico AL, Fouts TR, Shata MT, Kamin-Lewis R, Lewis GK, Hone DM

Division of Vaccine Research, Institute of Human Virology, University of Maryland Biotechnology Institute, 725 W. Lombard Street, Baltimore, MD 21201, USA.

Given the increasing incidence of HIV-1 infection world-wide, an affordable, effective vaccine is probably the only way that this virus will be contained. Accordingly, our group is developing an oral prime-boost strategy with the primary goal of eliciting broadly neutralizing antibodies against HIV-1 to provide sterilizing immunity for this virus. Our secondary goal is to elicit broadly cross-reactive anti-viral CD8(+) T cells by this strategy to blunt any breakthrough infections that occur after vaccination of individuals who fail to develop sterilizing immunity. This article describes our progress in the use of the live attenuated intracellular bacteria, Salmonella and Shigella, as oral delivery vehicles for DNA vaccines and the development of conformationally constrained HIV-1 Env immunogens that elicit broadly neutralizing antibodies.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983256, UI: 21980817

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Vaccine 2002 May 6;20(15):1961-3
 

The critical role of CD4(+) T-cell help in immunity to HIV.

Heeney JL

Department of Virology, Biomedical Primate Research Centre, P.O. Box 3306, 2280-GH Rijswijk, The Netherlands. heeney@bprc.nl

Vaccine-induced immunity to HIV/AIDS is a world wide health priority and a necessity in order to prevent or curb the transmission of this infection in the different human populations at risk. Failing to prevent infection, it would be desirable to generate sufficient immunity to control viremia in individuals which become infected, given that this would provide sufficient protection to prevent progression to AIDS. From several different pre-clinical settings data revealed that although CTL or neutralising antibodies were necessary immune responses for protection from infection, they were alone or together insufficient for providing solid protective immunity. What was invariably necessary was a strong specific CD4(+) T-cell response. Protective T-helper responses were not skewed towards an IFN-gamma (Th1) or IL-4 (Th2) type response, but were balanced and characterised by the presence of a strong Ag-specific IL-2 response.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983254, UI: 21980815

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Vaccine 2002 May 6;20(15):1927-32
 

Analysis of the immune response and viral evolution during the acute phase of SIV infection.

Horton H, Vogel T, O'Connor D, Picker L, Watkins DI

Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol City, Madison, WI 53715-1299, USA.

Development of an effective vaccine against human immunodeficiency virus (HIV) will require knowledge of the immune responses that correlate with protection. During the acute phase of HIV infection the host immune responses appear to control viral replication. It is thought that virus-specific cellular immunity is intimately involved in this viral control. We have developed a model system to measure the entire T cell response and viral evolution in the face of this onslaught in rhesus macaques during the acute phase of infection with molecularly cloned simian immunodeficiency virus (SIV). We used intracellular cytokine staining (ICS) of peripheral blood mononuclear cells (PBMCs) from animals during the acute phase of viral infection stimulated with peptides spanning the entire protein sequence of SIV to determine which peptides were recognized by CD8 and CD4 positive T cells. Furthermore, we sequenced the entire virus during the acute phase of infection. This approach has proved highly effective for measuring acute phase T cell responses and viral evolution in SIV-infected rhesus macaques and might facilitate the definition of cellular immune responses in HIV-infected humans during the acute phase.

PMID: 11983247, UI: 21980808

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Vaccine 2002 May 6;20(15):1922-5
 

Passive transfer studies to elucidate the role of antibody-mediated protection against HIV-1.

Mascola JR

Vaccine Research Center, NIAID/NIH, 40 Convent Drive, Bethesda, MD 20892, USA. jmascola@nih.gov

In order to understand immune correlates of protection and to develop effective immunization strategies, it is important to know if antibodies can confer protection against HIV-1 infection or disease. The recent development of the pathogenic simian/human immunodeficiency virus (SHIV)-macaque model based on env genes from primary HIV-1 isolates permits the in vivo evaluation of anti-HIV-1 envelope glycoprotein immune responses. Using this model, we and others initially showed that passively infused antibody can protect against an intravenous SHIV-challenge. However, HIV-1 is most often transmitted across mucosal surfaces and the intravenous challenge model may not accurately predict the role of antibody in protection against mucosal exposure. We, therefore, adapted the SHIV89.6PD model to allow evaluation of anti-HIV-1 antibodies against vaginal challenge. In order to make comparisons to our prior intravenous challenge study, we used the same SHIV89.6PD stock and antibodies. Our data show that antibodies can confer protection against vaginal exposure to a pathogenic SHIV; if virus transmission occurs, their presence can ameliorate the subsequent pathogenic manifestations of virus infection. Compared to our previous intravenous challenge study, greater protection was achieved after vaginal challenge. Because the highest level of protection occurred when the most potent combinations of antibodies were used, the data confirm that in vitro neutralization assays on peripheral blood mononuclear cells (PBMC) targets cells are a relevant measure of protective antibody activity.

Publication Types:
 

• Review
• Review, tutorial

PMID: 11983246, UI: 21980807

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Vaccine 2002 May 6;20(15):1895-2015
 

Nobel Symposium 119: Global HIV Therapeutics--HIV Vaccines. 7-9 June 2001, Stockholm, Sweden.

Publication Types:
 

• Congresses
• Overall

PMID: 11983239, UI: 21980800

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