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Updated: Dec 17, 2025
An Optimized Hemagglutination Inhibition HI Assay to Quantify Influenza-specific Antibody Titers
Published on: December 1, 2017
A randomized controlled trial of antibody response to 2018-19 cell-based vs. egg-based quadrivalent inactivated
Krissy K Moehling1, Richard K Zimmerman1, Mary Patricia Nowalk1
1Department of Family Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Insights
This study found no significant difference in immune response between cell-cultured inactivated influenza vaccine (ccIIV4) and egg-grown inactivated influenza vaccine (IIV4) in children and adolescents. Both vaccines demonstrated similar effectiveness in generating antibody titers against influenza strains.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Current influenza vaccine effectiveness (VE) improvement focuses on minimizing egg adaptation mutations during manufacture.
- This study compared the immune response of two FDA-approved quadrivalent inactivated influenza vaccines (ccIIV4 and IIV4) in healthy children and adolescents.
Purpose of the Study:
- To compare the immunogenicity of a cell-culture-derived inactivated influenza vaccine (ccIIV4) versus an egg-derived inactivated influenza vaccine (IIV4).
- To evaluate seroconversion rates, elevated titers, geometric mean titers (GMTs), and mean fold rise (MFR) in response to vaccination.
Main Methods:
- An unblinded, randomized controlled trial involved 144 healthy children and adolescents aged 4-20 years.
- Participants received either ccIIV4 (Flucelvax®) or IIV4 (Fluzone®).
- Hemagglutination inhibition (HI) and microneutralization (MN) assays were used to measure antibody titers pre- and post-vaccination.
Main Results:
- Low seroconversion rates (14%-35%) were observed and did not differ significantly between the ccIIV4 and IIV4 groups.
- No significant differences in other immunogenicity measures (elevated titers, GMTs, MFR) were found between the two vaccine types.
- Previously unvaccinated individuals showed higher MFR against certain strains compared to previously vaccinated individuals.
Conclusions:
- In this cohort of mostly older children with high baseline antibody titers, ccIIV4 and IIV4 demonstrated comparable immunogenicity.
- The findings suggest that both cell-culture and egg-based inactivated influenza vaccines induce similar immune responses in this population.
Background:
Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial.
Methods:
Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax®]; n = 85); or in egg medium (IIV4 [Fluzone ®]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio ≥ 4 with day 28 titer ≥ 40). Secondary outcomes were elevated titers (day 28 HI titer ≥ 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment.
Results:
In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients.
Conclusion:
In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses.
Clinical Trials No:
NCT03614975.
