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Emergence and Pathogenesis of Swine Influenza Viruses in Humans
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Jennifer L. Smith, Frederick T. Koster, Robert J. Hogan
The role of heterosubtypic immunity to influenza virus mediated either by nonneutralizing cross-reactive antibodies or by memory T cells is still the subject of debate in terms of human cases. Preexisting immunity may be one factor that accounts for lower death rates during influenza outbreaks. There has been speculation that persons >65 years of age may have experienced a more mild infection during the 1918 pandemic because they had partial immune protection from having been exposed to an H1N1 strain that circulated in the previous era. In addition, the CDC reported that about 33% of individuals >60 had preexisting cross-neutralizing antibodies against the 2009 pdmH1N1, but seasonal influenza vaccines did not elicit these cross-reactive neutralizing antibodies. These cross-neutralizing antibodies were elicited to an H1N1 circulating prior to 1957. Several studies suggested that the cross-reactivity was between the 1918 and 2009 pdmH1N1 viruses and that antibodies to the 1918 virus recognized the HA from both the 1918 and 2009 pdmH1N1.194 However, in young adults, the high titers of low-avidity, nonprotective antibodies were not able to completely block infection with the 2009 pdmH1N1 and instead accumulated in the lung triggering inflammation-mediated damage. These immune complexes may have accounted for the higher incidence of severe disease in this age group.195 Therefore, it is clear that infection or vaccination with 1918 H1N1 virus or 2009 pdmH1N1 and other influenza virus strains can result in the generation of antibodies and cross-reactive T cells that are functional in terms of cytokine secretion and cytotoxicity. This suggests that humans may possess some level of CD4+ and CD8+ T cell-mediated heterosubtypic immunity, depending upon the strain of virus encountered during the primary infection or vaccination.196–199 Taken together, clearance of influenza virus infection in the lungs requires an extremely complex interaction of innate and adaptive immune responses that is highly coordinated in the upper and lower respiratory tract, circulatory system, and lymphoid tissues.
Nasal delivery of H5N1 avian influenza vaccine formulated with GenJet™ or in vivo-jetPEI® induces enhanced serological, cellular and protective immune responses
Published in Drug Delivery, 2018
Weiping Cao, Margarita Mishina, Samuel Amoah, Wadzanai P. Mboko, Caitlin Bohannon, James McCoy, Suresh K. Mittal, Shivaprakash Gangappa, Suryaprakash Sambhara
Effective antibody response is essential to prevent influenza virus infection by blocking virus entry, but the optimal antibody response and ultimate elimination of the virus-infected cells require effector CD4 and CD8 T cells. Qin et al. (2015) showed that the activation and proliferation of total CD4 and CD8 T cells were increased by vaccination with H9N2 vaccine formulated with PEI (Qin et al., 2015). Our study further characterized the antigen-specific T cell response in mice immunized with H5N1 vaccine with or without GenJet™ or in vivo-jetPEI®. Both formulations substantially increased the frequency of antigen-specific cytotoxic CD8 T cells in the draining lymph nodes where T-cell activation was initiated. Activated T cells migrate from LN to the lungs where they eliminate virus-infected cells. After clearance, immunological memory is established both locally and systemically. The ability of CD8 T cells to recognize conserved viral genes is critical in conferring heterosubtypic immunity (Sridhar, 2016). In addition to the increased frequency of antigen-specific CD8 T cells, IFN-γ production by CD8 T cells was also slightly increased in the spleens of mice immunized with the formulated vaccine. Similar to CD8 T cells, the frequency of IFN-γ producing CD4 T cells were increased in mice that received the H5N1 vaccine formulated with GenJet™ or in vivo-jetPEI®. CD4 T-cell induction is required for the generation of protective antibody responses by B cell and expansion of antiviral CTL responses (Leist et al., 1987; Matloubian et al., 1994). Serum IgG isotype profiles were further characterized and the results showed that vaccine alone elicited more IgG1 (TH2 type response) production than IgG2a, IgG2b and IgG3 (TH1 type response), whereas the H5N1 vaccine formulated with GenJet™ or in vivo-jetPEI® induced a mixed TH1 and TH2 response. Wegmann et al. (2012) and Qin et al. (2015) both demonstrated that PEI-adjuvanted vaccines enhanced the innate responses including antigen uptake, DC migration, and maturation which subsequently increased the humoral and cellular immune responses.