Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?

Malosh, R. E.; Petrie, J. G.; Callear, A.; Truscon, R.; Johnson, E.; Evans, R. R.; Bazzi, L. A.; Cheng, C.; Thompson, M. S.; Martin, E. T.; Monto, A. S.

Background: The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort. Methods: Using longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households. Results: The pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (-6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccine coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VET was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households. Conclusion: Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.