Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease

Benoît, André; Beran, Jiřı́; Devaster, Jeanne Marie; Esen, Meral; Launay, Odile; Leroux‐Roels, Geert; McElhaney, Janet E.; Oostvogels, Lidia; Essen, G A van; Gaglani, Manjusha; Jackson, Lisa A.; Vesikari, Timo; Legrand, Catherine; Tibaldi, Fabián; Innis, Bruce L.; Dewé, Walthère

doi:10.1093/ofid/ofv067

Cited by 44 publications

(44 citation statements)

References 14 publications

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“…3C). HI titers have been shown to correlate with neutralizing activity (30) and with influenza immunity (31)(32)(33). All animals mounted HI titers of 1:80 or higher against H3-wt virus.…”

Section: Resultsmentioning

confidence: 96%

Immunodominance of Antigenic Site B in the Hemagglutinin of the Current H3N2 Influenza Virus in Humans and Mice

Broecker

Liu

Sun

et al. 2018

J Virol

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The hemagglutinin protein of H3N2 influenza viruses is the major target of neutralizing antibodies induced by infection and vaccination. However, the virus frequently escapes antibody-mediated neutralization due to mutations in the globular head domain. Five topologically distinct antigenic sites in the head domain of H3 hemagglutinin, A to E, have been previously described by mapping the binding sites of monoclonal antibodies, yet little is known about the contribution of each site to the immunogenicity of modern H3 hemagglutinins, as measured by hemagglutination inhibition activity, which is known to correlate with protection. To investigate the hierarchy of antibody immunodominance, five Δ1 recombinant influenza viruses expressing hemagglutinin of the A/Hong Kong/4801/2014 (H3N2) strain with mutations in single antigenic sites were generated. Next, the Δ1 viruses were used to determine the hierarchy of immunodominance by measuring the hemagglutination inhibition reactivity of mouse antisera and plasma from 18 human subjects before and after seasonal influenza vaccination in 2017-2018. In both mice and humans, mutations in antigenic site B caused the most significant decrease in hemagglutination inhibition titers compared to wild-type hemagglutinin. This study revealed that antigenic site B is immunodominant in the H3N2 influenza virus strain included in the current vaccine preparations. Influenza viruses rapidly evade humoral immunity through antigenic drift, making current vaccines poorly effective and antibody-mediated protection short-lived. The majority of neutralizing antibodies target five antigenic sites in the head domain of the hemagglutinin protein that are also the most sequence-variable regions. A better understanding of the contribution of each antigenic site to the overall antibody response to hemagglutinin may help in the design of improved influenza virus vaccines.

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“…3C). HI titers have been shown to correlate with neutralizing activity (30) and with influenza immunity (31)(32)(33). All animals mounted HI titers of 1:80 or higher against H3-wt virus.…”

Section: Resultsmentioning

confidence: 96%

Immunodominance of Antigenic Site B in the Hemagglutinin of the Current H3N2 Influenza Virus in Humans and Mice

Broecker

Liu

Sun

et al. 2018

J Virol

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“…В ранних работах было показано, что наличие в крови грипп-специфичных АТ с титром 1/40 по данным РТГА обеспечивает, по крайней мере, 50% снижение риска заражения гриппом в человеческой популяции [10,15]. Однако в более поздних исследованиях было установлено, что этот показатель может сильно варьировать в зависимости от возраста пациентов, характеристик популяции, типа вакцины и особенностей заболевания [4,5,8,22].…”

Section: Discussionunclassified

“…Оценка заболеваемости гриппом A(H3N2) показала, что для достижения одного и того же уровня протекции титр вирусспецифичных АТ, определенный в РТГА, должен быть более чем в 4 раза выше у людей старше 65 лет, по сравнению с более молодыми пациентами [4].…”

Section: Discussionunclassified

Microneutralization reaction compared to hemagglutination inhibition assay to evaluate immunogenicity of influenza vaccines and influenza diagnostics

Кривицкая¹,

Кузнецова²,

Maiorova³

et al. 2020

Russian Journal of Infection and Immunity

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The aim of this study was to compare the results of the hemagglutination inhibition test (HI-test) and microneutralization reaction in detection of antibodies to influenza A(H1N1), A(H1N1)pdm09, and A(H3N2) viruses in human sera, as well optimize microneutralization reaction conditions. The proposed variant of microneutralization reaction is based on detecting decreased influenza virus reproduction in infected MDCK cells in the presence of virus-specific serum antibodies. Virus reproduction was evaluated by enzyme-linked immunosorbent assay in 96-well cell culture plates using type-specific anti-influenza A viruse NP-protein monoclonal antibodies. In parallel, in microneutralization reaction and HI-test paired sera collected from 205 volunteers inoculated with inactivated seasonal influenza vaccines were analyzed, as well as from 117 adult patients with laboratory-confirmed influenza. The rationale for treatment of human serum with receptor-destroying enzyme (RDE) was proved not only for HI-test, but also for microneutralization reaction. Compared to HI-assay, the microneutralization reaction displayed higher sensitivity. According to microneutralization data, seroconversion rates and increase in antibody titer against influenza A viruses in both vaccinated and infected persons were superior to HI-test data by 1.4–2.5-fold. Moreover, higher sensitivity of this method was of great importance for the diagnostics of disease caused by new pathogens. The efficacy of influenza A(H1N1)pdm09 serodiagnostics in PCRpositive patients was 1.5 times higher based on microneutralization reaction vs. HI-assay data. According to the data from early studies, it is commonly believed that 1/40 titer of flu-specific antibodies detected by HI-test is set as protective. However, a consensus on protective level for virus-specific antibodies in neutralization reaction has not been established yet. It was found that serum antibody levels detected by the proposed version of microneutralization reaction were significantly higher than those in HI-assay. In the post vaccination sera collected from vaccinated volunteers, average titers of virus neutralizing antibodies corresponding to 1/40 in HI-test were 1/195, 1/203, and 1/ 426–1/430 for influenza A(H1N1), A(H1N1)pdm09 and A(H3N2), respectively, whereas in influenza patients they were 1/285, 1/215 and 1/488, respectively. Thus, it was suggested to consider a threshold value for “conditionally protective” level of neutralizing antibodies in adult vaccinated volunteers or infected patients, an average titer 1/160 for A(H1N1) and A(H1N1)pdm09 viruses, as well as 1/320 — for A(H3N2) virus, which agree with data published elsewhere.

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“…PT infants had higher peak HAI titers than FT infants to some vaccine antigens, and the peak serum titers correlated with the vaccine-specific ASC frequencies in all infants. There were few differences in the proportions of infants who reached protective titers, which are in any case only approximations of vaccine effectiveness [26, 28]. Both PT and FT infants had significant heterogeneity of the ASC subsets after the first influenza vaccine.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants

D’Angio

Wyman

Misra

et al. 2017

Vaccine

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Background Preterm (PT) infants are at greater risk for severe influenza infection and experience decrements in long-term antibody responses to vaccines. This may related to defects in antibody secreting cell (ASC) generation. Objective To investigate the relationships among the frequencies of influenza-specific antibody secreting cells ASC numbers and subsets and antibody responses to influenza vaccines (IV) among PT and full-term (FT) infants. Design/Methods We enrolled 11 former PT (≤32 weeks’ gestation, ≤1500 grams’ birth weight) and 11 FT infants, 6 to 17 months of age, receiving their first influenza immunizations. Infants received two doses of inactivated trivalent (T)IV or quadrivalent (Q)IV during the 2012–2013 and 2013–2014 influenza seasons, respectively, at 0 and 28 days, and blood was drawn at 0, 10, 35, and 56 days and 9 months. Vaccine-specific antibody was measured by hemagglutination inhibition (HAI) at 0 and 56 days and 9 months, vaccine-specific ASC numbers by enzyme linked immunospot (ELISPOT) at 10 and 35 days, and ASC subsets by flow cytometry at 0, 10 and 35 days. Results PT infants had post-vaccine HAI titers to all 4 vaccine strains at least equal to FT infants at 56 days and 9 months after beginning immunization. Influenza-specific ASC ELISPOT responses at 35 days were higher among PT than FT infants (median 100 v. 30 per 106 PBMC, p = 0.04). ASC numbers at 35 days were positively correlated with serum HAI titers at 56 days (ρ=0.50–0.80). There were no statistical differences between PT and FT infants in the frequency of five ASC subsets and no specific ASC subset correlated with durability of serum antibody titers. Conclusion(s) Influenza-specific ASC numbers in both FT and PT infants correlated with peak antibody titers, but ASC subsets did not correlate with durability of antibody response.

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Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease

Cited by 44 publications

References 14 publications

Immunodominance of Antigenic Site B in the Hemagglutinin of the Current H3N2 Influenza Virus in Humans and Mice

Immunodominance of Antigenic Site B in the Hemagglutinin of the Current H3N2 Influenza Virus in Humans and Mice

Microneutralization reaction compared to hemagglutination inhibition assay to evaluate immunogenicity of influenza vaccines and influenza diagnostics

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants

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