Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009-2014.

BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14-.44) or influenza virus (HR, 0.52; 95% CI, .38-.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062-.093), while men with influenza virus-positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.

Investigating the Legacy of the 1918 Influenza Pandemic in Age-Related Seroepidemiology and Immune Responses to Subsequent Influenza A(H1N1) Viruses Through a Structural Equation Model.

A(H1N1) strains of Influenzavirus were responsible for 2 pandemics in the last 100 years. Because infections experienced early in life may have a long-lasting influence on future immune response against other influenza strains, we drew on previously collected seroincidence data from Singapore (n = 2,554; June-October 2009) to investigate whether the 1918 pandemic influenza virus and its early descendants produced an age-related signature in immune responses against the A/California/7/2009(H1N1)pdm09 virus of 2009. Hemagglutination inhibition assays revealed a J-shaped relationship; the oldest birth cohort (born in 1911-1926) had the highest titers, followed by the youngest (born in 1987-1992). Differential response by vaccination history was also observed, with seasonal influenza vaccine being associated with higher titers mainly in the oldest birth cohort. On the assumption that antibody titers are a correlate of protection, structural equation modeling predicted that a titer-mediated effect by the vaccine could, on its own, account for a negative association with seroconversion equivalent to a risk reduction of 23% (relative risk = 0.77, 95% confidence interval: 0.60, 0.99) in the oldest birth cohort. A subset of 503 samples tested against the A/Brisbane/59/2007(H1N1) and A/Puerto Rico/8/1934(H1N1) strains also revealed different age-related antibody profiles. The effectiveness of seasonal influenza vaccines against future pandemic strains could thus be age-dependent and related to early-life exposures.