Results from our simulations suggest that vaccines effective against only 3 out of 4 circulating serotypes can lead to reductions even in scenarios where the serotype with low or zero efficacy (in this case DENV-2) is more pathogenic, more transmissible or experiences greater infectiousness enhancement. These findings indicate that vaccines effective against only three serotypes may have positive impacts at the population level, even under some of the adverse scenarios that led to recommendations to focus on the development of tetravalent dengue vaccines [26]. These results provide insight into the impact that competition between serotypes may have

on the overall efficacy of partially Cobimetinib mw effective vaccines and are consistent with previously published work [27]. Assuming that individuals can only undergo up to two infections, in hyperendemic settings (where 2 or more serotypes circulate) partially effective vaccines can lead to a decrease in competition

and increased transmission of serotypes for which the vaccine has low efficacy. The overall reduction in the number of clinical cases will depend on the pathogenicity of the serotypes that benefit from this reduced competition. Our results also show that vaccination might lead to a shift in the mean-age of cases toward younger age groups. If vaccine induced immunity enhances severity of infections among those that experience infection, vaccinating young immunologically naive children might predispose

them to clinically apparent disease earlier in life. This result might have important implications since severe dengue manifestations (dengue hemorrhagic fever and dengue shock syndrome) are thought Selleck BLZ945 to be more frequent and severe among infants and young children [28]. Finally, our results indicate that direct and indirect effects of a vaccine could differ, potentially resulting in non-vaccinees in a highly vaccinated population experiencing the greatest reductions in cumulative incidence of clinically apparent dengue. Much of this effect is dictated by the immunopathogenic effects of vaccine derived immunity that we assumed, and would not be observed if vaccine immunity conferred protection against clinical disease. While in all of these instances the cumulative incidence in vaccinees was lower than what it would have been before in the absence of vaccine, and the overall population effects were positive, this finding raises issues about the relevance of individual versus population protection. The use of incentives to promote vaccination may be used to manage expectation regarding specific benefits of vaccination vs. non-vaccination under different vaccination coverages [29] and [30]. Two other efforts have recently estimated the potential impact of a dengue vaccine [21] and [22]. Neither of these papers addresses the potential impact of vaccines that differ in their efficacy by serotype, a key feature of the vaccine reported by Sabchaereon et al. [1].