Open AccessFeatures of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine
Author(s) -
Л. М. Цыбалова,
Л. А. Степанова,
Marina A. Shuklina,
Alexandr V. Korotkov,
М. В. Зайцева,
В. И. Грищенко,
Р. Ю. Котляров
Publication year - 2019
Publication title -
infekciâ i immunitet
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.137
H-Index - 5
eISSN - 2313-7398
pISSN - 2220-7619
DOI - 10.15789/2220-7619-2019-3-4-485-494
Subject(s) - virology , vaccination , virus , immunization , immune system , biology , tlr5 , immunology , population , hemagglutinin (influenza) , flagellin , influenza a virus , inactivated vaccine , antibody , medicine , toll like receptor , innate immune system , receptor , biochemistry , environmental health
Generating cross-reactive vaccines aimed at targeting all human influenza A virus subtypes is among high priority tasks in contemporary vaccinology. Such vaccines will be primarily demanded during pre-pandemic period as well as used to prime some population cohorts prior to vaccination with standard vaccines containing area-relevant epidemic virus. Unlike routine approach universal vaccines do not induce a sterilizing immunity, but significantly ameliorate overt infection and probable complications. Our study was aimed at evaluating characteristics of immune response in experimental animals primed with a candidate universal vaccine challenged with sublethal influenza A virus infection. Mice were immunized intranasally with the recombinant protein FlgH2-2-4M2e containing conservative peptides derived from two influenza A virus proteins: M2 protein ectodomain and 76–130 amino acid sequence from the second hemagglutinin (HA2) subunit genetically linked to bacterial flagellin protein, which is a ligand for Toll-like receptor 5 (TLR5). Control mice received saline. Two weeks after immunization, mice from both groups were infected with a sublethal dose of A/Aichi/2/68 AN3N2 influenza virus strain. Level of immunoglobulins G and A in the blood sera and bronchoalveolar lavages (BAL) were determined two weeks after immunization and 1 month post infection. Percentage of lung CD4+ T and CD4+ Tem (CD44+CD62L–) cells secreting cytokines TNFα, IFNγ, IL-2 was determined. Immunized vs. control mice responded to sublethal infection with the influenza virus by insignificant weight loss and more pronounced production of vaccine peptide-specific (M2e and aa76–130 HA2) and pan-influenza A/Aichi/2/68 virus IgG and A in the blood sera and BAL. After challenge the number of CD4+ T cells secreting cytokines TNFα and/or IL-2 in immunized mice significantly exceeded counterpart T cells in unimmunized animals that was true for both CD4+T and CD4+ Tem cells. Memory CD4+ T cells were previously shown to play a key role in the prime-boost event and heterosubtypic immune response. Thus, we were able to demonstrate a priming effect for recombinant cross-protective vaccine used in our experiment.