Heterosubtypic Immunity to Lethal Influenza A Virus Infection Is Associated with Virus-Specific CD8+Cytotoxic T Lymphocyte Responses Induced in Mucosa-Associated Tissues

Abstract

Heterosubtypic immunity, defined as cross-reactive immune responses to influenza virus of a different serotype than the virus initially encountered, was investigated in association with virus-specific cytotoxic T lymphocyte (CTL) responses induced in systemic and mucosa-associated lymph nodes after immunization via different routes. Mice immunized by the pulmonary route with live nonpathogenic influenza virus, strain Udorn (H3N2), survived challenge with mouse-adapted pathogenic influenza virus, strain PR/8/34 (H1N1). These mice developed strong heterosubtypic CTL responses in spleen, cervical lymph nodes (CLN), and mediastinal lymph nodes (MLN). Alternately, only 20% of mice immunized intravenously, intraperitoneally, or intranasally survived the challenge; all of these developed CTL responses in spleen and CLN, but not in MLN. Direct correlation between short-term and long-term memory heterosubtypic CTL responses induced in MLN and host recovery after lethal infection indicates that these CTL responses may play an important role in heterosubtypic immunity. Furthermore, induction and maintenance of memory CTL in regional mucosa-associated lymphoid tissues are highly dependent on mucosal immunization. The results implicate the mechanism of heterosubtypic immunity and should be an important consideration in the development of protective mucosal vaccines against variant strains of influenza and HIV.

Intranasal lipopeptide primes lung‐resident memory CD8+ T cells for long‐term pulmonary protection against influenza

“…In that study, high levels of influenza-specific memory CD8 + T cells were achieved by sequential infection with heterologous influenza viruses. In the absence of a human-compatible live attenuated influenza vaccine that replicates within the lung to prime or boost CD8 + T cell immunity [16], it will be necessary to devise alternate strategies to achieve this goal. The results obtained with the i.n.…”

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

“…The latter has been shown to afford various degrees of protection in animal models and humans, depending on the combination of subtypes of IAV used for priming and challenge infection, respectively (Benton et al, 2001;Grebe et al, 2008;Kreijtz et al, 2007Kreijtz et al, , 2009McMichael et al, 1983;Nguyen et al, 1999;O'Neill et al, 2000;Schulman & Kilbourne, 1965;Seo & Webster, 2001). …”

Virus-specific intestinal IFN-γ producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs

“…calves and pigs [21][22][23]. However, because of the potentially important role for CD4+ and CD8+ T cells in rotavirus immunity, especially in heterotypic protection as suggested by studies of influenza virus infections [24], it is important to quantify and characterize antigen-specific CD4+ and CD8+ T cells in an animal model of rotavirus disease as well as in human clinical trials for the development of new rotavirus vaccines. The objective of this study was to identify the potential correlation between HRV-specific IFN-γ producing or proliferating T cell responses with protective immunity induced by rotavirus infection and vaccination using our well-established Gn pig model of HRV infection and disease [25,26].…”