Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya

Abstract

Streptococcus pneumoniae is the primary etiological agent of community-acquired pneumonia and a major cause of meningitis and bacteremia. Three conserved pneumococcal proteins-pneumolysin, pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein A (PspA)-are currently being investigated as vaccine candidates. Such protein-based vaccines, if proven effective, could provide a cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan Africa exist concerning the development of natural antibody to these antigens, however. To investigate the age-specific development of antiprotein immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2 weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked immunosorbent assays. IgG and IgA antibody responses to each antigen were observed in all age groups. Serum concentrations of IgG and IgA antibody responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but not to PsaA, increased significantly with age (P < 0.001). No decline was observed in the sera of the elderly. Anti-protein IgG concentrations were only weakly correlated (0.30 < r < 0.56; P < 0.0001), as were IgA concentrations (0.24 < r < 0.54; P < 0.0001).In Kenya, as in other developing countries, invasive pneumococcal disease (IPD) is responsible for substantial morbidity and mortality (6, 8). In populations for which incidence data are available, the risk of IPD peaks at the end of the first and beginning of the second year of life, declining sharply thereafter. Disease incidence remains low through puberty and early adulthood, rises gradually through middle age, and increases dramatically for individuals over 65 (15,18,23). Recent largescale efficacy trials have shown that a 7-valent pneumococcal conjugate vaccine is effective against IPD and, to a lesser extent, against pneumonia caused by vaccine types (3,12,17). Unfortunately, the price of this vaccine will likely preclude its inclusion in national immunization programs for many countries with the greatest burden of pneumococcal disease. Recent studies also suggest that coverage for such multivalent vaccines may not be universally optimal across the developing world (7, 9). Furthermore, it remains unclear whether serotype replacement will result in significant increases in non-vaccine-type disease in the face of widespread conjugate vaccine use (16). Streptococcus pneumoniae vaccines based on conserved pneumococcal protein antigens such as pneumococcal surface protein A (PspA), pneumolysin, and pneumococcal surface adhesin A (PsaA) are currently under study (4, 5) and, if proven effective, may provide an alternative that is less expensive while affording greater coverage.Immunity to PspA, pneumolysin, and PsaA in European adults and children with and without pneumococcal disease has been studied extensively (20)(21)(22). To the best of our knowledge, the development of naturally acquired immunity to these three antigens in an African population has not yet been described. In...

Serum and mucosal antibody responses to pneumococcal protein antigens in children:relationships with carriage status

“…Unlike the others, no further rise in anti-PsaA antibodies was seen after the age of 2 years. Studies in Finnish children have also shown early acquisition of detectable serum anti-PsaA antibodies and progressive rises in anti-Ply and -PspA antibodies over the first 24 months of life [13] and a closely similar pattern was also observed in a seroprevalence study in Kenya [32]. Both those studies and ours suggest either that in pneumococcal colonization, PsaA is more immunogenic than other antigens in the first year of life, or that anti-PsaA antibodies are induced by another non-pneumococcal cross-reacting antigenic stimulus.…”

Development of Antibodies to PspA Families 1 and 2 in Children after Exposure to Streptococcus pneumoniae

“…Studies suggested that infants and children develop only low or undetectable concentrations of serum and salivary anti-PspA antibodies after exposure to pneumococci (24,33). Similar kinetics were observed for Kenyan children: anti-PspA IgG and IgA developed later than antibodies to other surface proteins, with concentrations slowly increasing until early childhood (16). In the sera of young Filipino infants, antibodies to PspA were detected only rarely in spite of frequent pneumococcal colonization (13).…”

Effects of Ageing and Gender on Naturally Acquired Antibodies to Pneumococcal Capsular Polysaccharides and Virulence-Associated Proteins

“…Concentrations of immunoglobulin G (IgG) antibodies to pneumococcal capsular polysaccharides (PPS) have been found to remain unchanged or decrease by age, depending on the serotype and the study (1,33,35). Age-specific development of antibody concentrations to pneumococcal proteins PsaA, PspA, and pneumolysin from young to old has been assessed in a Kenyan study with no decline in ageing adults (20). No previous data are available on the concentrations of IgM antibodies to PPS in the elderly, but a dramatic decline in the numbers of IgM memory B cells has been found with ageing (38).…”