Comparison of neutralizing antibody and cell-mediated immune responses to pandemic H1N1 2009 influenza virus before and after H1N1 2009 influenza vaccination of elderly subjects and healthcare workers

Abstract

The recent H1N1 pandemic virus that emerged in 2009 resulted in high morbidity rates mainly in younger individuals, albeit with relatively low mortality. We investigated both humoral and cellular immune responses against the pandemic H1N1 2009 virus before and after immunization with inactivated H1N1 2009 vaccine. We obtained paired blood specimens from a cohort of participants from nursing homes (n=108) and a public hospital (n=60) in Singapore. Serum samples were tested for neutralizing antibodies against H1N1 2009 using microneutralization assays, while peripheral blood mononuclear cells were subjected to interferon-γenzyme-linked immunosorbent spot (ELISPOT) assays for whole virus-specific T-cell responses. We observed significant increases in geometric mean titers of neutralizing antibodies after H1N1 2009 vaccination (from 23.6 pre-vaccination to 94.7 post-vaccination). Approximately 77% and 54% of the cohort exhibited ≥2-fold and ≥4-fold increases in neutralizing antibody titers following vaccination; 89.9% of the cohort had a post-vaccination antibody titer of ≥32. Adjusted for gender, participants aged ≥60 years were less likely to have a ≥4-fold increase in antibody titers after vaccination than those aged <60 years (0.48; 95% confidence interval (95% CI) 0.32-0.71, p=0.007). There was a 1.4-fold elevation in H1N1 2009-specific T-cell responses after vaccination (p<0.05). Adjusted for gender, age ≥60 years was positively associated with a greater increase in T-cell response (β=4.9, 95% CI 1.58-8.29, p=0.018). No significant correlation was observed between humoral and cellular immune responses. Influenza vaccination elicits significant neutralizing antibody and T-cell responses to pandemic H1N1 2009 influenza virus. However, in response to vaccination, increases in neutralizing antibody titers were comparatively lower but T-cell responses were higher in older participants. Therefore, our study suggests that memory T-cells may play a crucial role in protecting older individuals against pandemic H1N1 2009 infection.