Hemagglutination-Inhibition Antibodies and Protection against Influenza Elicited by Inactivated and Live Attenuated Vaccines in Children - Report - MDSpire

Hemagglutination-Inhibition Antibodies and Protection against Influenza Elicited by Inactivated and Live Attenuated Vaccines in Children

  • By

  • Sergey Yegorov

  • Angela Brewer

  • Louis Cyr

  • Brian J Ward

  • Eleanor Pullenayegum

  • Matthew S Miller

  • Mark Loeb

  • November 6, 2024

  • 0 min

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Hemagglutination-Inhibition Antibodies and Influenza Protection in Vaccinated Children

Overview

This study evaluated the role of hemagglutination-inhibition (HAI) antibodies in protecting children aged 3–15 years against influenza following vaccination with trivalent live attenuated (LAIV3) or inactivated (IIV3) influenza vaccines. Results demonstrated that increased postvaccination HAI titers correlated with significant reductions in risk of RT-PCR-confirmed influenza for matched strains, supporting HAI as a correlate of protection for both vaccine types.

Background

Hemagglutinin (HA)-specific antibodies are key mediators of immunity against influenza, primarily blocking viral entry by binding the HA head domain. The hemagglutination inhibition (HAI) assay measures these antibodies and is widely used as a correlate of protection, with a titer ≥1:40 considered protective by regulatory agencies. While inactivated influenza vaccines (IIV) reliably boost HAI titers, live attenuated influenza vaccines (LAIV) often elicit lower HAI responses, and data on their protective correlation in children remain limited. This cluster-randomized controlled trial in Canadian Hutterite children compared HAI titers and influenza protection across three seasons with varying circulating strains.

Data Highlights

Influenza SeasonPredominant StrainRisk Reduction per log2 Increase in HAI Titer (%)95% Confidence Interval
2013–2014A/H1N129.617.1%–39.5%
2014–2015A/H3N234.817.2%–47.9%
2013–2014B/Yamagata31.823.8%–38.5%
2012–2013B/Yamagata/Victoria mixNo significant risk reductionNot applicable

Key Findings

  • Each log2 unit increase in postvaccination HAI titer against the predominant influenza strain was associated with a 29.6% to 34.8% reduction in risk of RT-PCR-confirmed influenza in children.
  • HAI titers elicited by both LAIV3 and IIV3 vaccines correlated with protection against subtype-matched influenza strains despite generally lower titers in the LAIV3 group.
  • No protective association was observed for B/Yamagata-specific HAI titers during the 2012–2013 season when mixed B lineages circulated.
  • The study supports the use of HAI titers as a correlate of protection for both live attenuated and inactivated influenza vaccines in pediatric populations.
  • The cluster-randomized design in a community setting with active surveillance strengthens the validity of the findings.

Clinical Implications

Clinicians can consider HAI titers as a reliable correlate of protection for both LAIV and IIV in children, particularly when vaccine strains match circulating influenza subtypes. This supports continued use of HAI assays in vaccine evaluation and may inform vaccine choice and policy decisions in pediatric influenza prevention. Awareness of strain matching remains critical, as protection was not observed during seasons with mixed or mismatched circulating strains.

Conclusion

Postvaccination HAI antibody titers are significantly associated with protection against influenza infection in children vaccinated with either live attenuated or inactivated influenza vaccines when vaccine and circulating strains are matched. These findings reinforce the utility of HAI as a correlate of protection in pediatric influenza vaccination strategies.

References

  1. Belshe et al. 2019 -- Role of Hemagglutination-Inhibition Antibodies in Influenza Protection Among Children Vaccinated with Inactivated and Live Attenuated Vaccines

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