Early life serological profiles and the development of natural protective humoral immunity to Streptococcus pyogenes in a high burden setting
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Streptococcus pyogenes leads to 500,000 deaths annually; many due to rheumatic heart disease in low-income settings. Limited understanding of natural protective immunity to S. pyogenes hinders vaccine development. We describe the evolution of serological profiles to conserved vaccine - antigens and type-specific M peptides from birth and throughout the life course in The Gambia. As placentally-transferred IgG waned after birth, serological evidence of new exposure was seen in 23% infants during the first year of life. Following culture-confirmed S. pyogenes events, the highest IgG increases occurred in children under two years following both pharyngeal and skin disease, and asymptomatic carriage at both sites. Higher IgG to conserved antigens SLO, SpyCEP and SpyAD correlated with functional activity and were associated with protection from culture-confirmed events following adjustment for age and anti-M protein IgG levels. Our data provide the first evidence of protection associated with humoral immunity to conserved vaccine candidate antigens in humans.
