Journal
CLINICAL INFECTIOUS DISEASES
Volume 71, Issue 12, Pages 3096-3102Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciz1198
Keywords
influenza hemagglutinin; influenza neutralizing antibodies; neuraminidase inhibition antibodies; correlates of protection; H3N2 subtype
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Funding
- US FDA
- Armed Forces Health Surveillance Branch/GEIS of the Department of Defense
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Background. Antibodies that inhibit hemagglutination have long been considered a correlate of protection against influenza, but these antibodies are only a subset of potentially protective antibodies. Neutralizing and neuraminidase antibodies may also contribute to protection, but data on their associations with protection are limited. Methods. We measured preoutbreak hemagglutinin pseudovirus neutralization (PVN) and neuraminidase inhibition (NAI) antibody titers in unvaccinated military recruits who experienced an H3N2 influenza outbreak during training. We conducted a case-control study to investigate the association between titers and protection against influenza illness or H3N2-associated pneumonia using logistic regression. Results. With every 2-fold increase in PVN titer, the odds of medically attended polymerase chain reaction-confirmed H3N2 infection (H3N2(+)) decreased by 41% (odds ratio [OR], 0.59; 95% confidence interval [CI], .45 to .77; P < .001). Among those who were H3N2(+), the odds for pneumonia decreased by 52% (OR, 0.48; CI, .25 to .91; P = .0249). With every 2-fold increase in NAI titer, the odds of medically attended H3N2 infection decreased by 32% (OR, 0.68; 95% CI, .53 to .87; P = .0028), but there was no association between NAI titers and H3N2-associated pneumonia. There was also no synergistic effect of PVN and NAI antibodies. Conclusions. PVN and NAI titers were independently associated with reduced risk of influenza illness. NAI titers associated with protection had greater breadth of reactivity to drifted strains than PVN titers. These findings show that PVN and NAI titers are valuable biomarkers for assessing the odds of influenza infection.
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