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Title: The effects of strain variation on respiratory syncytial virus infection and immunity
Author: Sande, Charles Jumba
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2013
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available