[HTML][HTML] Use of opsonophagocytosis for serological evaluation of pneumococcal vaccines

S Romero-Steiner, CE Frasch, G Carlone… - Clinical and Vaccine …, 2006 - Am Soc Microbiol
S Romero-Steiner, CE Frasch, G Carlone, RA Fleck, D Goldblatt, MH Nahm
Clinical and Vaccine Immunology, 2006Am Soc Microbiol
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 …
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 g/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. In the wake of the success of the conjugate vaccine (Prevnar; Wyeth Lederle Vaccines), new or improved pneumococcal vaccines for both children and adults are being actively developed. Future vaccine formulations may likely contain a higher number of capsular serotypes and may be formulated to also contain vaccines against other pathogens as part of a new combination vaccine. Evaluation of these vaccines would be heavily dependent on demonstrating that the new vaccines can also induce opsonic titers that are sufficient for protection. For these reasons, various forms of opsonization assays have been developed, and there have been significant technical improvements in pneumococcal antibody OPAs, such as the introduction of multiplexed OPAs. Thus, a workshop was held in Atlanta, Ga., on 5 June 2005 to discuss progress made for each methodology and discuss standardization of pneumococcal antibody opsonization assays. The workshop was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the World Health Organization, and the University of Alabama at Birmingham and was attended by various representatives from academia, industry, government agencies, and public reference laboratories. We present here a review of the current status of OPAs for anti-capsular polysaccharide antibodies as summarized during the workshop.
American Society for Microbiology