Abstract
Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes.
Highlights
® Belgium) and RotaTeq (Merck and Co., Whitestation, NJ, USA), are licensed in most countries around the world3. ® Group A Rotaviruses (RVAs) are double-stranded RNA viruses with a genome composed of 11 segments4,5
Rotavirus vaccination coverage with at least one dose increased from 0% to 75% during 2006, and the coverage with either vaccine has levelled off at approximately 86% (Fig. 1a,b, Fig. S1); only 79% of infants received a full course of either vaccine in 2012 (Fig. 1a, Fig. S1)
Since the start of vaccination, the number of rotavirus related hospitalizations recorded by Carenet-National Alliance of Christian Sickness Funds (NCSF) has decreased by 85% (Fig. 1a)
Summary
® Belgium) and RotaTeq (Merck and Co., Whitestation, NJ, USA), are licensed in most countries around the world3. ® Group A Rotaviruses (RVAs) are double-stranded RNA viruses with a genome composed of 11 segments. Despite the rather conserved nature of these human RVA genomes, the two outer capsid proteins, VP7 and VP4, are much more variable in comparison with the rest of the genome6 These two outer capsid proteins both elicit neutralizing antibodies, and are classified into distinct G- (VP7) and P- (VP4) genotypes. A recent study found strong statistical differences in the genotype distribution of vaccinated and unvaccinated children, with an increased prevalence of G2P[4] in vaccinated children in Belgium, suggesting that Rotarix may exert selective pressures on the viral population. The one strain-specific model for rotavirus demonstrated that the cycling of genotypes in the population could be explained by differences in homotypic and heterotypic immunity, and predicted that vaccination with a monovalent vaccine such as Rotarix could exert different pressures on the viral population than a vaccine that provided strong protection again all strains, such as RotaTeq. The model did not differentiate between Wa-like and DS-1-like rotavirus strains and the differences in immunity that may result
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