Immunogenicity and protective efficacy of prime-boost immunization in mice vaccinated with live and inactivated influenza A (H5N1) vaccines

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Avian influenza A (H1N1) in humans is characterized by severe clinical manifestation and high mortality. The main drawback of current human H5N1 vaccines is related to low immunogenicity. Prime-boost vaccination is considered as an effective approach to enhance vaccine immunogenicity. The aim of this study was to compare immune response and protective efficacy of diverse prime-boost immunization protocols: 1) prime and boost with live influenza vaccine (LAIV) А/17/Turkey/Turkey/05/133 (H5N2); 2) prime with LAIV А/17/Turkey/Turkey/05/133 (H5N2) followed by boost with inactivated influenza vaccine (IIV) “Orniflu” (H5N1). Both vaccination protocols were found to increase serum antibody level against homologous and heterologous influenza A virus strains. In particular, serum HAI antibodies were significantly elevated solely after LAIV/LAIV vaccination. A more sensitive sandwich ELISA assay revealed that serum virus-specific IgG antibody levels were significantly increased after both vaccination protocols as well as after a single LAIV or IIV vaccination. Both LAIV and IIV boost increased titers of serum IgG specific against unrelated influenza A (H5N1) strains: homologous A/NIBRG-23 (clade 2.2), A/Indonesia (clade 2.1) and, to a lesser extent, against clade 1 virus A/ Vietnam and even against heterologous А/New York (H1N1). Single LAIV vaccination was also able to induce antibody responses against all strains examined, though to a lesser degree as compared with either prime-boost protocols. However, amount of splenic CD8+  Тcells specific to homologous influenza A virus strain was solely observed after LAIV/IIV vaccination. Moreover, both LAIV and IIV boosting effect demonstrated high protection level against lethal challenge with А (H1N1) WT virus and significantly decreased lung viral titer compared to control group. Furthermore, both regimens resulted in lung virus clearance after non-lethal challenge with clade 1, 2.1 or 2.2 influenza А (H5N1). In conclusion, we demonstrated that both LAIV/LAIV and LAIV/IIV regimens were able to induce cross-clade A (H5N1) response and that prime-boost immunization was a promising approach to improve immunogenicity of influenza A (H5N1) virus vaccine.

About the authors

I. Losev

Institute of Experimental Medicine

ORCID iD: 0000-0002-5245-7315

Losev Igor. V. - Researcher, Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation

G. Petukhova

Institute of Experimental Medicine

ORCID iD: 0000-0001-9312-4739

Petukhova Galina D. - PhD (Biology), Senior Researcher, Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Phone: +7 (921) 759-96-06 (mobile).

Russian Federation

I. Isakova-Sivak

Institute of Experimental Medicine

ORCID iD: 0000-0002-2801-1508

Isakova-Sivak Irina N. - PhD (Biology), Head of the Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation

L. Rudenko

Institute of Experimental Medicine

Author for correspondence.
ORCID iD: 0000-0002-0107-9959

Rudenko Larisa G. - PhD, MD (Biology), Honored Worker of Science of the Russian Federation, Head of the Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation


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Copyright (c) 2019 Losev I., Petukhova G., Isakova-Sivak I., Rudenko L.

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