Repiratory Syncytial Virus (RSV)

A main focus of our current research is the transmission dynamics of respiratory syncytial virus, the major viral cause of infant and childhood severe pneumonia worldwide. RSV, as it is known, exhibits considerable genetic diversity (Groups A and B and within each a set of variants) which is apparently under immune selection. Occurrence of the virus is structured at the population level exhibiting sequential dominance of these variants; presumably resulting from (localised) strain specific herd immunity that provides competitive fitness to the least prevalent strains. The virus does not induce solid immunity, re-infection is the norm (though progressively less severe), and, as yet no vaccine appears to be on the horizon.

Sequential dominance of RSV Group A and B in Finland (left panels) and England and Wales (left panels). A two group deterministic model is fitted to raw data (upper panels) with observed and modelled dominance patterns (lower panels). Whte et al, Epidemiol Infect 2005; 133: 279-289.

The fascination of RSV to the investigator is that despite its rather simple structure (there are only two proteins - F and G - on the surface recognised by the immune system) its ecology is complex and poorly understood. Paradoxes prevail: (i) while strain variation is the result of selective immune pressure, selection acts on only one surface protein (G) and occurs despite high degree of homology of the F protein even between Groups and against which neutralising antibodies are raised; (ii) while recurrent epidemics clearly suggests (at least partial) immunity to re-infection, and epidemic structuring implies immunity to be variant specific, re-infection with the same strain can arise in two sequential epidemics and with different variants of the same Group within a single epidemic. (iii) While serum neutralising antibody to both G and F protein exists, and appears to be a correlate of protection, the virus is rarely found systemically, and strain specific neutralising activity of human convalescent sera has not been demonstrated. Most effort is being applied to develop live-attenuated vaccines to protect the most vulnerable age group which is children under 3 months is age - a time when the child is immunologically immature and where there is maximal presence of RSV specific maternal antibodies to interfere with the vaccine: unsurprisingly there are difficulties in balancing the needs of immunogenicity without reactogenicity.

Natural History of Respiratory Syncytial Virus infection. Weekly and cumulative cases of RSV (primary in red, secondary in green) in two birth cohorts followed through 4 epidemics 2002-2005 in Kilifi District, Kenya.

The questions raised by the many unknowns of RSV epidemiology lend themselves to a multi-focused approach. We are engaged in community-based studies of the natural history of RSV infection and disease, including studies of household transmission, school re-infections, and contact patterns using conventional and electronic tagging location methods. This work is coupled to mathematical modelling studies of antigenically diverse pathogens and of RSV control programmes . Furthremore we are engaged in molecular and immuno-epidemiological studies to investigate the importance of strains variation to patterns of parasite persistence and development of immunity to re-infection. The work is set in framework of surveillance of severe paediatric pneumonia for multiple respiratory viruses within a well characterised study population. This programme of research is a collaboration between Warwick (Graham Medley), the Health Protection Agency (Pat Cane) and the KEMRI-Wellcome Trust Research Programme in Kilifi.