Biological properties of the recombinant influenza A/H1N1pdm09 virus expressing a fragment of the Streptococcus pneumoniae surface protein

Abstract

BACKGROUND: Live influenza vaccine strains may serve as a promising system for the delivery of target antigens to the body because such a vaccine is administered intranasally and stimulates multiple chains of immunity against both the target pathogen and the influenza virus, a serious infection that causes significant socioeconomic damage worldwide each year.

AIM: The study was aimed to evaluate the biological properties of a recombinant live influenza vaccine strain of subtype A/H1N1pdm09 expressing a fragment of the Streptococcus pneumoniae Spr1875 surface protein.

MATERIALS AND METHODS: The A/H1N1pdm09 recombinant live influenza vaccine strain expressing a 69-amino-acid fragment of the S. pneumoniae surface protein Spr1875 as part of a chimeric hemagglutinin molecule was prepared by reverse genetics using an 8-plasmid system. The reproductive activity of the recombinant virus was studied in chicken embryos, whereas immunogenicity and protective efficiency were studied in Balb/C mice.

RESULTS: The recombinant influenza virus strain with hemagglutinin H1-Spr-69 demonstrated active reproduction in chicken embryos and retained the temperature-sensitive phenotypic trait of vaccine viruses. However, its growth in the respiratory tract of mice was limited compared with the original A/H1N1pdm09 vaccine virus. Intranasal administration of the recombinant H1-Spr strain to mice resulted in stimulation of virus-specific serum IgG antibody production comparable to that induced by the classic live influenza A/H1N1pdm09 vaccine. Furthermore, this strain induced an increase in IgG antibodies against the pneumococcal insertion Spr1875. Although the A/H1N1pdm09 variant was more effective than the chimeric H1-Spr virus in preventing weight loss in mice infected with mouse-adapted influenza A/California/07/09 (H1N1)pdm09 (H1N1)pdm09 virus, the titers of the challenge virus in the lungs of mice from both vaccine groups were significantly reduced compared with unvaccinated animals.

CONCLUSIONS: The results demonstrate the ability of the chimeric recombinant H1-Spr strain to stimulate protective immunity against influenza virus.

Keywords

live influenza vaccine / recombinant influenza virus / A/H1N1pdm09 pandemic strain / Streptococcus pneumoniae

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