Cellular immune responses to recurring influenza strains have limited boosting ability and limited cross-reactivity to other strains

Abstract

Influenza vaccine provides protection against infection with matched strains, and this protection correlates with serum antibody titres. In addition to antibodies, influenza-specific CD8+ T-lymphocyte responses are important in decreasing disease severity and facilitating viral clearance. Because this response is directed at internal, relatively conserved antigens, it affords some cross-protection within a given subtype of influenza virus. With the possibility of a broader A(H1N1) Mexico outbreak in the fall of 2009, it appeared worthwhile studying the degree of cellular immune response-mediated cross-reactivity among influenza virus isolates. The composition of the 2006-2007 influenza vaccine included the A/New Caledonia/20/1999 strain (comprising a virus that has been circulating, and was included in vaccine preparations, for 6-7 years) and two strains not previously included (Wisconsin and Malaysia). This combination afforded us the opportunity to determine the degree of cross-reactive cellular immunity after exposure to new viral strains. We analysed the antibody responses and the phenotype and function of the T cell response to vaccine components. The results obtained show that antibody responses to A/New-Caledonia were already high and vaccination did not increase antibody or cytotoxic T lymphocyte responses. These data suggest that repeated exposure to the same influenza stain results in limited boosting of humoral and cellular immune responses.

Conserved epitopes dominate cross‐CD8+T‐cell responses against influenza A H1N1 virus among Asian populations

“…Moreover, we demonstrated that partial cross‐recognition can also be detected between the nonconserved peptides from 2009 pH1N1 and seasonal IAV. However, the disaccord between the antigenicities of the epitopes derived from 2009 pH1N1 and seasonal influenza viruses are also observed . Gras et al investigated the cross‐T‐cell responses against the HLA‐B7 supertype‐restricted variable epitope NP 418–426 in humans and found that cross‐reactive CD8 + T‐cell immunity exists between the pandemic 2009 pH1N1 and H1N1‐1918 IAV but not with current seasonal influenza viruses.…”

Seroprevalence of Pandemic (H1N1) 2009 in Pregnant Women in China: An Observational Study

“…Accordingly, vaccination with the same pH1N1strain would be needed for the naturally infected population in our study to acquire enough immunity. In addition, memory T cells also play a role in the cellular immune response to secondary infection [28]: flu-specific CD8+T-lymphocyte responses are important in decreasing disease severity and facilitating viral clearance [29], and CD4+ T cells are able to mediate potent antibody-independent antiviral immunity [28], [30]. Thus, the impact of the significant decline in seropositive rates of antibodies on the protection against secondary infection of the naturally infected population needs further investigation.…”

Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host

“…The limited ability of vaccination to significantly increase pre-existing influenza-specific T cells has been previously reported although the mechanism for this phenomenon has not yet been fully elucidated. 30,31 A potential mechanism could be the exhaustion of influenza-specific T cells upon repeated stimulation with the same influenza antigens. 32 Combining cellular and humoral measures of vaccine efficacy may increase the ability to predict the risk of influenza illness.…”