Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort

The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8log₁₀ PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9log₁₀ PRNT_, P=0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8log₁₀ PRNT_, P<0.0001), 1.0-1.9 (2.5log₁₀ PRNT, P<0.0001), and 2.0-2.9 (2.3log₁₀ PRNT, P<0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0log₁₀ PRNT, P=0.052). The early serum neutralizing response to secondary infection (3.02log₁₀ PRNT) was significantly greater than the early primary response (1.9log₁₀ PRNT, P<0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (∼3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history.