HUMAN IMMUNE RESPONSE TO POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES

多糖蛋白结合疫苗的人体免疫反应

• 批准号: 6162482
• 负责人: R SCHNEERSON
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162482
• 关键词: Shigella vaccines; Streptococcus vaccine; active immunization; bacterial polysaccharides; bactericidal immunity; chronic renal failure; clinical research; clinical trial phase I; drug screening /evaluation; human subject; immunoconjugates; immunoglobulins; infant human (0-1 year); laboratory mouse; sickle cell anemia; tetanus toxoid

Surface polysaccharides of pathogenic bacteria, including capsular polysaccharides and lipopolysaccharides, may serve as virulence factors amd protective antigens. The age-related immunogenicity and T-cell independence of polysaccharides limit their use as vaccines. Binding to medically-useful proteins both increases their immunogenicity and confers T-cell dependence to these polysaccharides. Infants were injected with Pn6B-TT at 3, 4 and 6 months of age or at 7 and 9 months of age with only minor local reactions. Anti-Pn6 of the three Ig classes, with booster responses, were induced. There was a good correlation between IgG anti-type 6B levels and opsonophagocytic killing of the organism in-vitro. LPS of Shigella sonnei and flexneri 2a were detoxified, their O-specific polysaccharides bound to bacterial toxoids and shown to be immunogenic in mice. Phase 1 and Phase 2 studies showed these conjugates were safe and elicited long-lived antibodies at similar levels to those of adult patients following shigellosis. In a Phase 3 trial, S. sonnei-rEPA protected army recruits during outbreaks of shigellosis caused by this pathogen. These conjugates were shown to be safe and immunogenic in 4-7 year old children. Phase 3 trials have been postponed while new and more immunogenic Shigella conjugates are being evaluated in Phase 1 studies. A double mutant of Bordetella pertussis, producing a non-toxic CRM toxin and deficient in FHA synthesis, is being developed. The objective is to use this genetically-produced and more easily purified pertussis toxoid as a carrier for pneumococcus type 14 polysaccharide. Infants immunized with Pn6B-TT responded with anti-Pn6B, mostly of the IgG isotype. These antibodies had opsonophagocytic activities, correlated to their levels as measured by ELISA and RIA.

致病菌的表面多糖，包括荚膜