B‐ and T‐cell memory elicited by a seasonal live attenuated reassortant influenza vaccine: assessment of local antibody avidity and virus‐specific memory T‐cells using trogocytosis‐based method

Abstract

Please cite this paper as: Petukhova et al. (2011) B‐ and T‐cell memory elicited by a seasonal live attenuated reassortant influenza vaccine: assessment of local antibody avidity and virus‐specific memory T‐cells using trogocytosis‐based method. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00279.x. Purpose The main purpose of vaccination is to generate immunological memory providing enhanced immune responses against infectious pathogens. The standard and most commonly used assay for influenza vaccine immunogenicity evaluation is a hemagglutination inhibition assay (HAI). It is clear now that HAI assay is unable to properly assess the proven protective immunity elicited by live attenuated influenza vaccines (LAIV). New methods need to be developed for more accurate LAIV immunogenicity assessment and prediction of vaccine efficacy among target populations. Objective Randomized placebo‐controlled study of memory B‐ and T‐cell responses to intranasal LAIV in young adults. Methods A total of 56 healthy young adults 18–20 years old received seasonal monovalent LAIV. Mucosal memory B‐cell responses were measured by IgA avidity assessment in nasal swabs. CD4 memory T cells in peripheral blood were examined by the expression of CD45RO marker and in functional test by the ability of virus‐specific T cells to maintain the trogocytosis with antigen‐loaded target cells. Results Intranasal LAIV immunization enhances mucosal IgA avidity even without reliable increases in antibody titers. At the day 21 after vaccination, up to 40% of subjects demonstrated significant increases in both total and virus‐specific CD4 memory T cells that were observed regardless of seroconversion rate measured by HAI assay. Conclusion The data suggest that immunogenicity of LAIV vaccines should be evaluated on the mucosal and cellular immunity basis. The assays applied could be used to support influenza clinical trials through preliminary screening of volunteers and subsequent measurement of anti‐influenza in immunity.

Successes and failures of the live-attenuated influenza vaccine, can we do better?

“…Furthermore, the antigenic distance we used is based on the serum hemagglutination inhibition (HI) assay. This has been historically used to measure the immune response to IIV, but there is increasing evidence that other assays measuring mucosal humoral responses might be better indicators of the LAIV immunogeniticy [61][62][63][64]. As more data becomes available on the antibody responses to different epitopes on the hemagglutinin and other proteins of influenza it may be possible to develop strategies that focus on the generation of responses to conserved eptiopes such as those on the stem of hemagglutinin and thus generate a universal influenza vaccine which avoids problems associated with strain variation [65][66][67][68].…”

Assessment of Human Immune Responses to H7 Avian Influenza Virus of Pandemic Potential: Results from a Placebo–Controlled, Randomized Double–Blind Phase I Study of Live Attenuated H7N3 Influenza Vaccine

“…LAIV strains developed at the IEM and based on seasonal [20] , pandemic [21] or viruses with pandemic potential [22] were shown to be able to stimulate CD4 + and CD8 + T cells. The same observation is presented here for H7N3 LAIV.…”

Vaccinating High-Risk Children with the Intranasal Live-Attenuated Influenza Vaccine: the Quebec Experience

“…Immunogenicity assays, such as hemagglutination inhibition assay, which measure systemic antibody response is inadequate to assess the protective immunity from LAIV: a recent paper showed that LAIV enhanced mucosal IgA avidity (specific local antibodies) in the absence of reliable increases in serum antibody titres. In that study, up to 40% of subjects demonstrated a significant increase in total and virus-specific CD4 memory T cells regardless of immunogenicity results [12]. Immunogenicity of LAIV should thus be evaluated at the mucosal level.…”