Malosh, R. E. | Search bioRxiv

bioRxiv2018

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population.

BackgroundInfluenza vaccines are important for prevention of influenza-associated hospitalization. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness evaluations in hospitalized populations.\n\nMethodsSerum specimens collected at admission from adults hospitalized for treatment of acute respiratory illnesses during two influenza seasons were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated the suitability of these specimens as proxies for pre-infection immune status, and measured associations between antibody titers and influenza vaccination and infection\n\nResultsSpecimens were collected within 3 days of illness onset from 65% of participants; geometric mean titers (GMTs) did not vary by day of collection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated participants. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016.\n\nConclusionsSerum collected after hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.

epidemiology↗

bioRxiv2017

The evolutionary dynamics of influenza A virus within and between human hosts

The global evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define the dynamics of influenza A virus populations in human hosts through next generation sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected over 5 seasons from individuals in a prospective community-based cohort, they are broadly representative of natural human infections with seasonal viruses. We used viral sequence data from 35 serially sampled individuals to estimate a within host effective population size of 30-70 and an in vivo mutation rate of 4x10-5 per nucleotide per cellular infectious cycle. These estimates are consistent across several models and robust to the models' underlying assumptions. We also identified 43 epidemiologically linked and genetically validated transmission pairs. Maximum likelihood optimization of multiple transmission models estimates an effective transmission bottleneck of 1-2 distinct genomes. Our data suggest that positive selection of novel viral variants is inefficient at the level of the individual host and that genetic drift and other stochastic processes dominate the within and between host evolution of influenza A viruses.

microbiology↗