Broad antibody and T cell reactivity induced by a pneumococcal whole-cell vaccine

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• 作者：Kristin L. Moffitt^a ; Puja Yadav^a ; Daniel M. Weinberger^b ; Porter W. Anderson^a ; Richard Malley^a ; ^{richard.malley@childrens.harvard.edu}
• 关键词：WCV ; whole cell vaccine ; Al(OH)3 ; aluminum hydroxide ; CWPS ; cell wall polysaccharide ; MLST ; multilocus sequence typing ; PCV ; pneumococcal conjugate vaccine ; MFI ; mean fluorescence intensity
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：19 June, 2012
• 卷：30
• 期：29
• 页码：4316-4322
• 文件大小：394 K

摘要

Injecting mice with killed cells of non-capsulated strain RM200 adsorbed on Al(OH)3 (pneumococcal whole-cell vaccine; WCV) reduces nasopharyngeal colonization by capsular serotype 6B and prevents fatal aspiration pneumonia by serotype 3 or serotype 5 strains. To further examine the potential for omni-strain immunity, we here examined a panel of clinical isolates and a library of capsule-switch variants in the TIGR4 background. IgG binding to these bacteria in sera of rabbits injected with WCV or Al(OH)3 alone was assayed by ELISA without and with adsorption with cell-wall polysaccharide, a species-common antigen. The examined strains were 23 primary isolates including at least 10 different MLS types and 13 serotypes; 15 of these strains were invasive isolates, subsequently mouse-passed. Additionally, to investigate the effect of capsulation, TIGR4 strain constructs with the capsulation genes of 20 different serotypes were evaluated. In ELISA all strains showed a large difference in IgG binding due to the immunization, of which most of the antibody typically was not CWPS-adsorbed and presumably directed to exposed protein antigens. Increased binding of IgG in the WCV-immunized serum to the 20 isogenic capsule-switch strains was shown also by flow cytometry. Further, all these 20 strains elicited IL-17A in T cells of WCV-vaccinated mice, a cytokine known to accelerate pneumococcal clearance. Thus WCV induced both humoral and T_H17 cell-mediated immunity against all tested strains.