The Effects of Strain Variation on Respiratory Syncytial Virus Infection and Immunity

Sande, Charles Jumba (2013). The Effects of Strain Variation on Respiratory Syncytial Virus Infection and Immunity. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f0ba

Abstract

Introduction: The transmission of RSV in the human population is characterised by seasonal epidemics displaying cyclic alternation in dominance of the two antigenic groups A and B. The mechanisms that underlie this population-level competition between RSV A and B, and heterogeneity in transmission fitness of RSV genotypes are not clearly defined. The dynamics of neutralising antibody response following birth and primary infection as well as pro- and anti- inflammatory cytokines/chemokines following natural infection in infants, especially in relation to RSV antigenic variation, have not been well characterised.

Methods: Neutralising antibodies were measured in the acute and convalescent sera of infants with RSV-associated pneumonia as well as from a birth cohort. Additionally, 10 cytokines/chemokines were measured in nasal secretions obtained from infants recruited within the household setting and from whom samples were obtained twice weekly during an RSV epidemic.

Results: The proportion of RSV A infected individuals seroconverting to a contemporary group A test virus was significantly higher than the proportion seroconverting to a contemporary group B virus (p=0.0005). The proportion of RSV B infected individuals seroconverting to a contemporary group B virus was higher than the proportion seroconverting to a contemporary A virus (p=0.008). The mean duration of maternal neutralising antibodies above a putative protective threshold was 2.8 months (95%CI 2.5-3.1 months). Primary neutralising antibodies declined to pre-infection levels within 3-4 months. The levels of some cytokines/chemokines correlated with viral load but not with RSV group.

Conclusion: The data suggest that population-level competition between RSV A and B is related to development of transient group-specific immunity following natural infection. Thus it might be argued that future RSV vaccines should include strains from both groups in order to maximise the indirect protective effect of a vaccination programme. No evidence was found for strain-specificity in cytokine/chemokine responses following RSV infection.