Abstract
Pneumococcal vaccine development is driven by the achievement of high activity in a single gatekeeper assay: the bacterial opsonophagocytic killing (OPK) assay. New evidence challenges the dogma that anti-capsular antibodies have only a single function that predicts success. The emerging concept of multi-modal protection presents an array of questions that are fundamental to adopting a new vaccine design process. If antibodies have hidden non-opsonic functions that are protective, should these be optimized for better vaccines? What would protein antigens add to protective activity? Are cellular immune functions additive to antibodies for success? Do different organs benefit from different modes of protection? Can vaccine activities beyond OPK protect the immunocompromised host? This commentary raises these issues at a time when capsule-only OPK assay-based vaccines are increasingly seen as a limiting strategy.
Highlights
The development of vaccines has historically placed great emphasis on three gold standard functional assays of antibody activity: the opsonophagocytic killing (OPK) and serum bactericidal assays for bacteria and the neutralization assay for viruses
This commentary addresses the question, “In an era recognizing a need for broader anti-pneumococcal vaccines that protect against old and newly recognized aspects of disease, should measuring vaccine efficacy be modified by adding other assays of functions of both capsules and proteins as immunogens?” We posit that capsular polysaccharide and protein immunogens have much broader bioactivities in terms of both quantity and quality of immune functions, which can be targeted and harnessed as better vaccines are developed
IgA, the polymeric form of the antibody, is capable of contributing to pathogen control through agglutination, as well as by facilitation of complement-mediated killing [70–72]. These systemic and site-specific IgA responses are not currently measured by the standard OPK assay and, we suggest, would be valuable measures of vaccine efficacy at the mucosal sites
Summary
The development of vaccines has historically placed great emphasis on three gold standard functional assays of antibody activity: the opsonophagocytic killing (OPK) and serum bactericidal assays for bacteria and the neutralization assay for viruses. A growing body of evidence indicates that this single-minded approach is passé, and that can anti-polysaccharide antibodies do much more than enable OPK, but new protein antigens can be protective even in the absence of neutrophils This commentary addresses the question, “In an era recognizing a need for broader anti-pneumococcal vaccines that protect against old and newly recognized aspects of disease, should measuring vaccine efficacy be modified by adding other assays of functions of both capsules and proteins as immunogens?” We posit that capsular polysaccharide and protein immunogens have much broader bioactivities in terms of both quantity and quality of immune functions, which can be targeted and harnessed as better vaccines are developed
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