Neutralizing stalk antibody responses during natural influenza

Identification: Perera, R.A.P.M.



Neutralizing stalk antibody responses during natural influenza
R.A.P.M Perera, B.J. Cowling, J.S.M. Peiris
School of Public Health, The University of Hong Kong
Introduction: Pre-existing neutralizing antibodies against hemagglutinin(HA) is a known determinant of protection against influenza. One such humoral immune response is the antibodies generated against stalk of the HA. Here, we explore kinetics of natural stalk responses.
a) Compare magnitude increase in group 1 and group 2 stalk antibody in those sero-convert to pandemic H1N1, seasonal H1N1and H3N2.
b) Investigate longitudinal stalk titers(2009-2014) and compare with corresponding HI titers.
c) Measure stalk titers in age groups ranging 2-80yrs.
Method: Acute and convalescent sera from PCR confirmed infections with 2009 pandemic influenza, seasonal H1N1 and seasonal H3N2 infection were utilized. Longitudinal cohort of 800 individuals spanning all ages were used for measuring longitudinal and age specific stalk responses.
Results: 3000 sera from 798 individuals were investigated. In 337 individuals that comprised seroconverters and non-seroconverers, there were 50 that showed ≥4 fold titer rise in group 1 responses. Highest number 27,(33.7%) group 1 stalk seroconverstions occurred in 2009 pandemic seroconverters, followed by 10(10.7%) in seasonal H1 and 3(5.5%) in seasonal H3 (P<0.01,99%CI). These results were similar trend as PCR confirmed data. Interestingly, 10(6.6%) were in non-seroconverters. Nine had group 2 ≥4 fold titer rise. Group 1 longitudinal responses show a highly significant boost after 2009 pandemic, then slight drop and afterwards the trend appears to be stable. Longitudinal group 2 response appears to be incrementally rising. Group 1 responses are significantly higher in 61-70 age decade(p<0.001) compared to all age groups. Interestingly for group 2 somewhat reverse trend observed where age groups “2-18” and “19-30” have significantly higher GMT titers(p<0.001).
Conclusion: A virus carrying novel HA head domain is capable of boosting stalk antibody responses during natural influenza infection of human. However, the stalk antibody responses are not induced to a higher level during seasonal vaccination. This indicates novel vaccination strategies that could elicit broadly neutralizing stalk responses are useful in pandemic preparedness. The kinetics of stalk antibody responses during natural infection can inform the design of novel vaccination methods.



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