Projecting the population-level impact of norovirus vaccines.

Norovirus diversity has major implications for vaccine design. The number of circulating genogroups and genotypes, and the way this viral diversity interacts at the population level, will factor into how many and which genotypes should be included in an effective vaccine. Here, we develop an age-stratified, multi-strain model for norovirus to project potential population-level impacts of different vaccine formulations on genotype-specific and overall annual attack rates. Our model assumes that vaccination impacts susceptibility to infection but not infectiousness or the risk of developing disease. We parameterize the baseline model (without vaccination) based on literature estimates and the ability to recover observed epidemiological patterns. We then simulate this model under seven different potential vaccine formulations, initially assuming only pediatric vaccination. While we find that increases in coverage result in declines in annual norovirus attack rates for all formulations considered, we also find that vaccine formulations that include genotype GII.4 would be most effective at lowering overall norovirus attack rates. Inclusion of additional genotypes in a vaccine would further lower attack rates but more incrementally, with the addition of GI.3, GII.2, GII.3, and GII.6 together having a similar impact to that of GII.4 alone on reducing overall norovirus incidence. We further find that transient dynamics are expected for 10-20 years following roll-out with any pediatric vaccine. During this time, there may be unanticipated changes in genotype circulation patterns, although long-term increases in non-vaccine genotype attack rates above baseline levels are not expected. Finally, we anticipate that annual vaccination of older-aged individuals with a GII.4-containing vaccine can, under certain conditions but not others, provide appreciable direct benefits to individuals in this age group beyond what pediatric vaccination affords. Together, our results indicate that there is a clear population-level benefit of primary pediatric vaccination with a GII.4-inclusive norovirus vaccine plus incremental value of other genotypes, with additional direct benefits of annual vaccination to older adults provided that vaccination results in a considerable (multi-month) duration of broadly protective immunity to infection. More empirical studies are needed to validate the structure of the model and refine its parameterization, both of which affect projections of vaccine impact.