Influenza H7N9 LAH-HBc virus-like particle vaccine with adjuvant protects mice against homologous and heterologous influenza viruses

Dan Zheng; Shaoheng Chen; Di Qu; Jianjun Chen; Fuyan Wang; Ran Zhang; Ze Chen

doi:10.1016/j.vaccine.2016.11.026

Influenza H7N9 LAH-HBc virus-like particle vaccine with adjuvant protects mice against homologous and heterologous influenza viruses

Vaccine. 2016 Dec 12;34(51):6464-6471. doi: 10.1016/j.vaccine.2016.11.026. Epub 2016 Nov 17.

Authors

Dan Zheng¹, Shaoheng Chen¹, Di Qu², Jianjun Chen³, Fuyan Wang⁴, Ran Zhang⁵, Ze Chen⁶

Affiliations

¹ Shanghai Institute of Biological Products, Shanghai 200052, China.
² Biosafety Level-3 Laboratory, Fudan University, Shanghai 200032, China.
³ State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
⁴ Department of Immunology, Xiangya School of Medicine, Central South University, Changsha 410078, China.
⁵ Medical College, Hunan Normal University, Changsha 410013, China.
⁶ Shanghai Institute of Biological Products, Shanghai 200052, China; Medical College, Hunan Normal University, Changsha 410013, China. Electronic address: chenze2005@hotmail.com.

PMID: 27866773
DOI: 10.1016/j.vaccine.2016.11.026

Abstract

The long alpha-helix (LAH) region located in influenza virus hemagglutinin (HA) shows conservation among different influenza A strains, which could be used as a candidate target of influenza vaccines. Moreover, the hepatitis B virus core protein (HBc) is a carrier for heterologous epitopes in eliciting effective immune responses. We inserted the LAH region of H7N9 influenza virus into the HBc and prepared the LAH-HBc protein, which were capable of self-assembly into virus-like particles (VLP), by using E. coli expression system. Intranasal immunization of the LAH-HBc VLP in combination with chitosan adjuvant or CTB^∗ adjuvant in mice could induce both humoral and cellular immune responses effectively and provide complete protection against lethal challenge of homologous H7N9 virus or heterologous H3N2 virus, as well as partial protection against lethal challenge of heterologous H1N1 virus. These results provide a proof of concept for LAH-HBc VLP vaccine that would be fast and easy to be produced and might be an ideal candidate as a rapid-response tool against a future influenza pandemic.

Keywords: Adjuvant; H7N9; Influenza; LAH-HBc VLP.

MeSH terms

Adjuvants, Immunologic / administration & dosage
Administration, Intranasal
Animals
Antibodies, Viral / blood
Chitosan / administration & dosage
Cross Protection*
Disease Models, Animal
Drug Carriers
Epitopes / genetics
Epitopes / immunology
Escherichia coli / genetics
Escherichia coli / metabolism
Female
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Hepatitis B Core Antigens / genetics
Influenza A Virus, H3N2 Subtype / immunology
Influenza A Virus, H7N9 Subtype / genetics
Influenza A Virus, H7N9 Subtype / immunology*
Influenza Vaccines / administration & dosage
Influenza Vaccines / genetics
Influenza Vaccines / immunology*
Leukocytes, Mononuclear / immunology
Mice, Inbred BALB C
Orthomyxoviridae Infections / prevention & control*
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Vaccines, Virus-Like Particle / administration & dosage
Vaccines, Virus-Like Particle / genetics
Vaccines, Virus-Like Particle / immunology*

Substances

Adjuvants, Immunologic
Antibodies, Viral
Drug Carriers
Epitopes
Hemagglutinin Glycoproteins, Influenza Virus
Hepatitis B Core Antigens
Influenza Vaccines
Recombinant Fusion Proteins
Vaccines, Synthetic
Vaccines, Virus-Like Particle
Chitosan