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At least 433 records · Page 24Linked to original sources
PubMed1997

Host immunobiology and vaccine development.

As the rules of immunoregulation become clearer, the design of vaccines and adjuvants is becoming more scientific. To understand these rules, the interactions between three kinds of cells need to be grasped. Antigen-presenting cells (APCs) initiate the immunoglobulin cascade. The most important of these are dendritic cells, which must first capture antigen, a process aided by particulate matter, the presence of natural or acquired antibodies, or the capacity to activate complement. Then T cells become activated through conjoint action of processed antigenic peptides and APC surface and secreted molecules. T cells mediate inflammation, develop cytotoxic capacity, and help in antibody formation. Whether cells of type 1 or type 2 predominate influences the direction of both cellular and humoral responses. B cells are then activated, leading to antibody formation and often to better antigen presentation. Both T and B cell memory, embedded in long-lived lymphocyte populations, aid heightened immune reactivity when the antigen is re-encountered. The best vaccines stimulate strong memory.

Antibody Formation↗
PubMed1997

Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development.

Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.

Amino Acid Sequence↗
PubMed1995

Induction of specific immunity at mucosal surfaces: prospects for vaccine development.

We have demonstrated the feasibility of studying antigen-specific immune responses in a variety of mucosal tissues in humans after vaccination and during infection. In this respect, we have documented the usefulness of both oral cholera and ETEC vaccines for assessing in functional terms specific subpopulations of B- and T-cell immunocytes during an immune response initiated and/or expressed in human mucosal tissues. Circulating specific IgA antibody-secreting cells in blood appear to reflect recent or ongoing antigen exposure of mucosal surfaces. This implies that the detection of such cells in blood, the most accessible lymphoid compartment in humans, represents the simplest way to assess the immunogenicity of mucosal vaccines and to supplement the diagnostic and monitoring of active mucosal infections. Our studies indicate that while the concept of an integrated mucosal immune network is clearly operational in humans (at least in regards to induction of secretory antibody responses), its generalization appears somewhat simplistic as illustrated by the compartmentalization of immune responses initiated in certain mucosal organs such as the small intestine and the tonsils. Finally, the potential of the cholera toxin B subunit as a carrier for delivery of chemically or genetically linked foreign epitopes for induction of disseminated mucosal immune responses raises hope for the development of broadly applicable vaccines to control mucosal infections.

Animals↗
PubMed1996

Acellular pertussis vaccines developed in Japan and their application for disease control.

Acellular pertussis vaccines, comprising mainly pertussis toxin and filamentous hemagglutinin (FHA) and used successfully in Japan since 1981, were evaluated. Anti-pertussis toxin antibody responses in children immunized with acellular pertussis vaccines were comparable or higher than in convalescent-stage patients with pertussis, while those for anti-FHA were far higher. Reactogenicity was much less than with whole cell pertussis vaccines: Fever > or = 38 degrees C occurred in 2%-4% of vaccinees; there was little redness > or = 5 cm in diameter at the vaccination site with the first dose but occurred in 7%-8% of vaccinees with subsequent doses. The estimated efficacy of acellular pertussis vaccine in children ages 2-8 years was 84% (95% confidence interval, 71%-91%). Since vaccine-induced immunity weakens after 6-10 years, adults are now a major source of pertussis transmission. The source of infection was an adult in 11.2% (10/89) of cases, and the secondary attack rate was 10.3% (19/185). Immunization with acellular pertussis vaccines for both adults and children is recommended for disease control.

Adult↗
PubMed1995

Genetic detoxification of bacterial toxins: a new approach to vaccine development.

Chemically detoxified bacterial toxins (toxoids) have been successfully used as vaccines for the prevention of many bacterial infectious diseases. Today, nontoxic derivatives of bacterial toxins can be obtained by mutagenesis of the toxin genes. These genetically inactivated toxins are superior to the classical toxoids both in safety and in immunogenicity and therefore they should replace the old toxoids in the existing vaccines. In addition, they represent a novel class of immunogens with unique properties, some of which may be used for innovative approaches to vaccination.

Antigen Presentation↗
PubMed2002

Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam.

OBJECTIVE: To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally. METHOD: Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer. FINDINGS: No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer. CONCLUSION: It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest.

Administration, Oral↗
PubMedDate not supplied

Attenuated live fowl cholera vaccine. I. Development of vaccine strain M3G of Pasteurella multocida.

A live cholera vaccine was developed from a virulent avian septicemia strain of Pasteurella multocida serotype 1. The virulent parental strain was mutagenized with N-methyl-N'-nitro-N-nitroso guanidine. Mutants were selected that had either smaller colonies at 37 C or temperature sensitivity for growth at 41 C. Four small-colony mutants and 2 temperature-sensitive mutants were studied. All the mutants were avirulent for turkeys. Sixteen days after turkeys were vaccinated with each mutant, both the vaccinates and unvaccinated controls were challenge-exposed to virulent P. multocida of the homologous serotype and the heterologous serotype 3. Two of the small-colony mutant strains protected against both homologous and heterologous challenge. Suggested for a live cholera vaccine is P. multocida M3G, a small-colony-forming mutant, innocuous for both mice and turkeys and stable against reversion.

Animals↗
PubMed1990

Homotypic and heterotypic epitope-specific antibody responses in adult and infant rotavirus vaccinees: implications for vaccine development.

Sera from infants and adults who received a live, attenuated monovalent rotavirus vaccine of serotype 1, 2, 3, or 4 VP7 specificity and rhesus rotavirus (RRV) VP4 specificity were analyzed for serotype-specific antibody responses by an epitope blocking immunoassay (EBA) and by neutralization. Although the assays correlated well, responses to the individual neutralization proteins or to different defined antigenic sites on the same protein could be distinguished only by EBA. In general, adult vaccinees exhibited both a homotypic response to the immunizing strain and a heterotypic response to other serotypes. Infant vaccinees less than 6 months old also had a homotypic antibody response but developed significantly fewer heterotypic responses than adults (1.2% and 59%, respectively; P less than .0001). In addition, postvaccination sera from vaccinees who developed naturally occurring rotavirus diarrhea during an efficacy trial of RRV (MMU-18006) or RIT 4237 vaccine were analyzed for serotype-specific responses. The data suggest that the inability to mount a heterotypic antibody response to the infecting serotypes in young infants may have been an important factor in failure of the vaccines to induce protection.

Adult↗