Screening for Th17-Dependent Pneumococcal Vaccine Antigens: Comparison of Murine and Human Cellular Immune Responses
Abstract
Conjugate vaccines against Streptococcus pneumoniae have significantly reduced the incidence of diseases caused by the serotypes included in those vaccines; however, there is still a need for vaccines that confer serotype-independent protection. In the current study, we have constructed a library of conserved surface proteins from S. pneumoniae and have screened for IL-17A and IL-22 production in human immune cells obtained from adenoidal/tonsillar tissues of children and IL-17A production in splenocytes from mice that had been immunized with a killed whole-cell vaccine or previously exposed to pneumococcus. A positive correlation was found between the rankings of proteins from human IL-17A and IL-22 screens, but not between those from human and mouse screens. All proteins were tested for protection against colonization, and we identified protective antigens that are IL-17A dependent. We found that the likelihood of finding a protective antigen is significantly higher for groups of proteins ranked in the top 50% of all three screens than for groups of proteins ranked in the bottom 50% of all three. The results thus confirmed the value of such screens for identifying Th17 antigens. Further, these experiments have evaluated and c...Continue Reading
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