Evaluating virus interference in a trial of influenza vaccination

Abstract

Introduction: Influenza vaccination is one of the most effective intervention to control disease transmission. However, it is hypothesized that influenza virus infection can provide short-lived non-specific immunity against other respiratory virus infections. Therefore, influenza vaccination could increase the risk of other respiratory virus infections, by preventing influenza virus infections and the consequent non-specific immunity. We aim to test this hypothesis and quantify the degree of such temporal protection. Methods: We analyzed data from a randomized controlled trial with 796 children to receive influenza vaccine or placebo in 2010. Swab samples were collected when participants reported symptoms associated with respiratory virus infections, and tested by multiplex array to identify influenza B and non-influenza respiratory virus infection. We developed an individual-based model that described the risk of non-influenza respiratory virus infection as depending on the infection status and time of influenza virus infection, to quantify temporal protection. Results: The direct protection against influenza and non-influenza respiratory virus infection from influenza vaccination was 64% (95% credible interval (CrI): 31%, 83%) and -5% (95% CrI: -38%, 20%) respectively. The risk of infection of non-influenza respiratory virus infection after an influenza virus infection was 52% (95% CrI: 7%, 76%) lower, compared with before an influenza virus infection. Assuming the protection only lasted 21 and 28 days, the degree of such protection was 70% and 78%, but they were not statistical significant. Among children <18 years, younger age (≤10 years) was associated with 72% (95% CrI: 31%, 125%) higher risk of non-influenza respiratory virus infection compared with older age. Conclusion: Influenza vaccination may has an limited impact on the risk of non- influenza respiratory virus infection. There could be non-specific immunity against respiratory virus infections from influenza virus infections, but the duration of such protection needs further research to confirm.