The open circles and corresponding whiskers indicate the mean titer within a particular stratum and 95% confidence intervals

The open circles and corresponding whiskers indicate the mean titer within a particular stratum and 95% confidence intervals. < 0.0001), 1.0C1.9 (2.5 log10 PRNT, < 0.0001), and 2.0C2.9 (2.3 log10 PRNT, < 0.001) months post-infection, and (iii) no different in sera collected at between NQDI 1 3.0 and 3.9 months post-infection (2.0 log10 PRNT, = 0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, < 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. Keywords: RSV, neutralizing antibody dynamics, immunity INTRODUCTION A recent review highlighted the significant burden of severe acute lower respiratory tract disease attributable to respiratory syncytial virus (RSV) [Nair et al., 2010]. Understanding the duration of neutralizing antibody responses following natural exposure will inform future control strategies by providing estimates of the duration of a key correlate of protective NQDI 1 immunity. Acquired and maternally derived neutralizing antibodies to RSV appear to correlate well with protection from severe disease [Eick et al., 2008; Glezen et al., 1981; Piedra et al., 2003] and re-infection [Hall et al., 1991; Lee et al., 2004]. NQDI 1 Despite development of these responses, RSV does infect individuals repeatedly [Hall et al., 1976; Henderson et al., 1979] suggesting that protective immunity is of short duration or that the virus through antigenic variation is capable of escaping protective immune responses or both mechanisms are at play. The duration of protection from infection and disease provided by both maternally-derived and acquired neutralizing antibody in early infancy is not well quantified, although a recent study shows that the risk of re-infection is significantly reduced for 6 months following primary infection [Ohuma et al., 2012]. Although previous studies have shown that serum antibody responses acquired following primary infection with RSV decline to pre-infection levels within a year [Ochola et al., Sstr5 2009; Welliver et al., 1980] antibody detection in these studies has been based on enzyme linked immunosorbent assays (ELISAs) or indirect immunofluorescent antibody techniques. These methods detect the total antibody response and not the neutralizing NQDI 1 response which may be a better correlate of protective immunity. The effect of variation in population-level virus transmission on population-level immunity has not been investigated exhaustively. Studies on the temporal relationship between neutralizing antibodies of maternal origin and population-level virus transmission have shown that population-level neutralizing antibodies decline in the absence of exposure and increase following an increase in virus transmission at the population-level [Stensballe et al., 2009], implying that a decline in herd immunity may establish the conditions necessary for the spread of the virus in the population. In the current study, the duration of neutralizing antibody responses to RSV was investigated and the relationship between population-level transmission and the kinetics of the neutralizing antibody response were analyzed. Determination of the duration of the neutralizing antibody response following natural exposure will provide important information on the potential effectiveness of future vaccine programs in reducing virus transmission and consequently the burden of RSV disease. MATERIALS AND METHODS Nasal samples from which the test viruses were derived were inoculated onto HEp-2 cells, incubated at 33C and examined daily for development of cytopathic effect. An immunofluorescent antibody test (IFAT; Millipore, Billerica, MA) was used to verify isolation of the virus in culture. Virus quantitation was done.