Superior In Vitro Stimulation of Human CD8+ T-Cells by Whole Virus versus Split Virus Influenza Vaccines

Abstract

Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

Innate Responses Induced by Whole Inactivated Virus or Subunit Influenza Vaccines in Cultured Dendritic Cells Correlate with Immune Responses In Vivo

“…However, WIV induced higher upregulation of activation markers and increased production of cytokines as compared to SU vaccine. These results are consistent with previous studies by us and others ([ 8 , 21 ]. Moreover, the gene signature induced by WIV profoundly differed from the gene signature induced by SU.…”

Induction of Local Secretory IgA and Multifunctional CD4+ T‐helper Cells Following Intranasal Immunization with a H5N1 Whole Inactivated Influenza Virus Vaccine in BALB/c Mice

“…We have previously demonstrated that mice immunized intramuscularly with a whole inactivated H3N2 virus vaccine displayed high serum IgG2a antibody levels, indicative of a Th1 profile which with time and after the second immunization became a more mixed Th1/Th2 profile . Vaccines containing novel avian subtypes have generally been poorly immunogenic . Further work with an intramuscularly administered candidate pandemic avian whole inactivated H7N1 virus vaccine resulted in much lower levels of circulating antibodies .…”

“…There are three main formulations of inactivated vaccines: whole virus, split virus and subunit inactivated vaccines . The whole virus vaccine is highly immunogenic and is still used in some countries, but most vaccines produced after the 1970s have been split or subunit, due to the increased reactogenicity observed when using whole virus vaccines . Split and subunit vaccines are less reactogenic than whole virus vaccines, but remain immunogenic despite the removal of internal viral components .…”

Reassortant viruses for influenza vaccines: is it time to reconsider their genome structures?

“…Nucleoprotein (NP) and matrix 1 (M1) protein have been identified as major targets of immunodominant CD4 + and CD8 + T-cell responses [6,7], and the T-cell immunity induced upon vaccination can explicate the superior protection afforded by split vaccines than protection by subunit vaccines which lack NP and M1 [8]. Whole-virion vaccines, in turn, are considered more immunogenic and cross-reactive than split vaccines due to the better structure of vaccine antigens that can be much more effectively presented by dendritic cells and macrophages to T cells through MHC-class I and II restricted manner [9].…”