Defining the vaccination window for respiratory syncytial virus (RSV) using age-seroprevalence data for children in Kilifi, Kenya

Abstract

BackgroundRespiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in early life and a target for vaccine prevention. Data on the age-prevalence of RSV specific antibodies will inform on optimizing vaccine delivery.MethodsArchived plasma samples were randomly selected within age strata from 960 children less than 145 months of age admitted to Kilifi County Hospital pediatric wards between 2007 and 2010. Samples were tested for antibodies to RSV using crude virus IgG ELISA. Seroprevalence (and 95% confidence intervals) was estimated as the proportion of children with specific antibodies above a defined cut-off level. Nested catalytic models were used to explore different assumptions on antibody dynamics and estimate the rates of decay of RSV specific maternal antibody and acquisition of infection with age, and the average age of infection.ResultsRSV specific antibody prevalence was 100% at age 0-<1month, declining rapidly over the first 6 months of life, followed by an increase in the second half of the first year of life and beyond. Seroprevalence was lowest throughout the age range 5–11 months; all children were seropositive beyond 3 years of age. The best fit model to the data yielded estimates for the rate of infection of 0.78/person/year (95% CI 0.65–0.97) and 1.69/person/year (95% CI 1.27–2.04) for ages 0-<1 year and 1-<12 years, respectively. The rate of loss of maternal antibodies was estimated as 2.54/year (95% CI 2.30–2.90), i.e. mean duration 4.7 months. The mean age at primary infection was estimated at 15 months (95% CI 13–18).ConclusionsThe rate of decay of maternal antibody prevalence and subsequent age-acquisition of infection are rapid, and the average age at primary infection early. The vaccination window is narrow, and suggests optimal targeting of vaccine to infants 5 months and above to achieve high seroconversion.

Seroepidemiology of respiratory syncytial virus in western India with special reference to appropriate age for infant vaccination

“…Though RSV disease burden is seen in infants less than 5 months age, in view of the possibility of interference of maternal antibodies with the vaccine‐induced immune response, 6 months seems to be the appropriate age for vaccination, whenever available. In Kenya, 25% of subjects at ~6 months age were antibody positive increasing to 43% at 9 months and 100% from 3 years onwards; birth status was not considered . RSV vaccine immunization at greater than 5 months was suggested.…”

“…Previous studies using catalytic models have determined appropriate age for vaccination. On the basis of the samples collected from Kenya (2007‐2010) and Brazil (1996), the vaccination windows were suggested to be 4.7 to 15.1 and 3.3 to 19.1 months respectively. Clearly, epidemiology of RSV directs immunization strategies for individual countries.…”

Approaches to use the WHO respiratory syncytial virus surveillance platform to estimate disease burden

“…RSV-associated infection is known to be very common as shown with ad hoc age-stratified serological studies, for example a study in Kenya indicated that 100% of the population are likely to be infected by 3 years of age. 3 Only a proportion of these infections, however, will be symptomatic and a smaller proportion of them will present to health services. In a prospective cohort study in Finland, the average annual symptomatic RSV infection rate was 275/1000 in children <3 years of age over two RSV seasons, of whom 58% developed acute otitis media, and only 3% of those symptomatic were hospitalized.…”

A multifaceted approach to RSV vaccination

“…12,59,67 Most of the RSV neutralizing activity is undetectable in infants who are 4-6 month of age. 66,67 The mechanism by which the level of antibodies (neutralizing or not) influences repression of RSV immunity is still not clear.…”