The association between age and the development of respiratory syncytial virus neutralising antibody responses following natural infection in infants

Abstract

To determine the age at which infants mount significant neutralising antibody responses to both natural RSV infection and live vaccines that mimic natural infection, RSV-specific neutralising antibodies in the acute and convalescent phase sera of infants with RSV infection were assayed. Age-specific incidence estimates for hospitalisation with severe RSV disease were determined and compared to age-specific neutralising antibody response patterns. Disease incidence peaked at between 2 and 3.9 months of life. Following natural infection, relative to the mean acute phase antibody titre, the mean convalescent titre was lower in the 0-1.9 month age class, no different in the 2-3.9 month age class and greater in all age classes greater than 4 months. These data suggest effective vaccination with live vaccines that mimic natural infection may not be achieved before the age of 4 months. Maternal vaccination may be an alternative to direct infant vaccination in order to protect very young babies.

Keywords: Immunity; Neutralising antibody; Respiratory syncytial virus.

Fig. 1

(a) The relationship between acute and convalescent phase titres with age. Mean acute phase titres are depicted by the black filled boxes (with corresponding 95% confidence intervals) while mean convalescent phase titres are shown in grey filled boxes (with 95% confidence intervals). The p values above each mean acute/convalescent pair indicate whether the mean differences in titre are statistically significant. The values below the acute/convalescent pair are the number of individuals in each age class whose acute/convalescent responses were analysed. (b) Comparison between age-specific incidence estimates of admission with severe disease and the ability to generate a neutralising antibody response following natural infection. The incidence of admission with RSV associated pneumonia within the Kilifi Health and Demographic Surveillance System (with corresponding 95% confidence intervals) is shown in the grey bars while the mean fold change in neutralising antibody titre from the acute to convalescent phases of infection are depicted using the black filled boxes (with corresponding 95% confidence intervals). The horizontal dashed line indicates a 1-fold change in titre; above which a rise in titre is observed and below which a decline in titre is observed. The solid horizontal line indicates the 4-fold level that is used to define a seroconversion. The p values against the vertical dashed lines connecting the mean fold changes in titre to the horizontal dashed line indicating a 1-fold change in titre indicate whether the age-specific mean fold changes in titre are significantly different from 1. The association between age-specific incidence estimates of disease and fold changes in titre from the acute to convalescent phases of infection is not causal.

Fig. 2

The increase in the magnitude of the neutralising antibody response with age. The percentage of all infants within specific age classes with any rise in titre (**) and the proportion of infants who seroconverted (*) following natural infection is shown. The vertical lines indicate the fold change in titre from the acute to convalescent phases of infection. Each panel header indicates the age class being analysed as well as the number of individuals in that age class. Responses greater than unity indicate rises in titre following infection, while those below indicate decline in titre. Responses that are equivalent to or greater than a 4-fold rise in titre (dashed line) are considered to be seroconversions.