Pneumococcal vaccine and opsonic pneumococcal antibody

Abstract

Streptococcus pneumoniae is a major human pathogen responsible for a majority of bacterial pneumonia as well as invasive pneumococcal diseases (IPD) with high mortality and morbidity. Use of conjugate vaccines targeting pneumococcal capsule has dramatically reduced the incidence of invasive diseases and there are active efforts to further improve the conjugate vaccines. However, in children new pneumococcal vaccines can no longer be tested with placebo-based clinical trials since effective vaccines are currently available. Thus, vaccine studies must depend on surrogate markers of vaccine efficacy. Although traditional antibody levels (e.g., ELISA) are useful as a surrogate marker of protection, they have limitations and a bioassay measuring the capacity of antibodies to opsonize pneumococci has been developed. This opsonophagocytosis assay (OPA) replicates the in vivo mechanism of antibody protection and should therefore better reflect protection by vaccine-induced antibodies. Technical improvements of OPA have made this bioassay rapid, multiplexed and practical for analyzing small samples including those from children. Strong correlations between ELISA and OPA have been observed in many studies of young children. However, poor correlations have been found in some important clinical situations (such as determination of protection by cross-reactive antibodies) and populations (such as elderly adults and immune-deficient patients). In these settings, OPA has become a useful supplementary measure of pneumococcal vaccine immunogenicity. Current efforts to standardize OPA will further expand its uses.

Pneumococcal Capsules and Their Types: Past, Present, and Future

“…PPV23 covers a wider array of serotypes than current PCVs (Table 2) and could thus theoretically prevent ϳ73% of IPD based on 2007 American serotype distributions (143); however, it has some limitations. First, PPV23 is poorly immunogenic in infants younger than 2 years of age (123,162). Second, it showed poor effectiveness against nonbacteremic or community-acquired pneumonia (163) and against IPD in chronically ill patients (163) and individuals aged 75 years or older (164).…”

“…The poor immunogenicity of PPV in infants younger than 2 years led to the development of PCVs (162,173,174). PCVs are made by conjugating PSs to proteins, but their immunogenicity may be determined by the protein carrier, the method of conjugation, the ratio of PS to carrier, the length of the saccharide chains (PS versus oligosaccharide), and the quantity of PS (175).…”

Streptococcus pneumoniae Serotype 1 Burden in the African Meningitis Belt: Exploration of Functionality in Specific Antibodies

“…Currently, it is uncertain to what extent seroprevalence data reliably predict the protection of naive populations to pneumococcal disease. While over-or underestimations of clinical effectiveness based upon IgG data have been published in vaccine studies (13,27), some disagreements between clinical observations (carriage or infection) and naturally induced pneumococcal seroprevalence have been reported in large epidemiological surveys. In Burkina Faso, Yaro et al (11) suggested that all serotypes, regardless of their prevalence in carriage or IPD, had similar patterns of IgG seroprevalence.…”

Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

“…A strong antibody response does not necessarily reflect upon the protection of an individual (38). In this regard, functional assays are preferred, such as the OPA, a recognized correlate of protective immunity against extracellular encapsulated Gram-positive bacteria (18,92). During the OPA, opsonizing antibodies from the immunized serum will opsonize the target bacteria, which results in bacterial phagocytosis and bactericidal activity (38,(93)(94)(95).…”

“…As the CPS is the most external bacterial layer in contact with the host, antibodies against it are highly opsonizing and protective, as demonstrated for several encapsulated pathogens (17)(18)(19)(20). Paradoxically, due to their carbohydrate nature, CPSs are in general considered poorly immunogenic and do not generate long-lasting adaptive immune responses.…”