Use of opsonophagocytosis for serological evaluation of pneumococcal vaccines

Since 2000, when a pneumococcal conjugate vaccine (Prevnar) was introduced, pneumococcal infections in the United States among children have been dramatically reduced. The conjugate vaccine elicits antibodies to pneumococcal capsular polysaccharide, and these antibodies protect the host by opsonizing pneumococci and thus facilitating phagocytosis. The ability of a serum sample to opsonize bacteria can be measured by various in vitro opsonophagocytosis assays (OPAs), and OPAs have been shown to be the best functional correlate of protection in various studies. A minimum opsonic titer of 1:8 confers protection in a mouse model, is correlated with protection in infants vaccinated with pneumococcal conjugate vaccine, and was shown in infants to correspond to an immunoglobulin G (IgG) antibody concentration of 0.2 to 0.35 µg/ml (5). A Finnish study with an 11-valent pneumococcal conjugate vaccine conducted in the Philippines showed a good correlation between an opsonophagocytic killing assay and the IgG antibodies as measured by enzyme-linked immunosorbent assay (ELISA) (12), although the correlation may be limited in some populations, as described later in this review.