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

Abstract

Background: Influenza vaccines are important for prevention of influenza-associated hospitalization. However, the effectiveness of influenza vaccines can vary by year and influenza type and subtype and mechanisms underlying this variation are incompletely understood. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness in hospitalized populations.

Methods: We enrolled adults hospitalized for treatment of acute respiratory illnesses during the 2014-2015 and 2015-2016 influenza seasons whose symptoms began <10 days prior to enrollment. Influenza infection status was determined by RT-PCR. Influenza vaccination status was defined by self-report and medical record/registry documentation. Serum specimens collected at hospital admission were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated how well antibody measured in these specimens represented pre-infection immune status, and measured associations between antibody and influenza vaccination and infection.

Results: Serum specimens were retrieved for 315 participants enrolled during the 2014-2015 season and 339 participants during the 2015-2016 season. Specimens were collected within 3 days of illness onset from 65% of participants. Geometric mean titers (GMTs) did not vary by the number of days from illness onset to specimen collection among influenza positive participants suggesting that measured antibody was representative of pre-infection immune status rather than a de novo response to infection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated. 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.

Conclusions: Serum collected shortly after illness onset at 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.

Keywords: Correlates of protection; Hemagglutinin; Influenza; Influenza vaccine; Inpatient; Neuraminidase; Serology.