Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice

Autor: Wai-Lan Wu, Songzhi Gu, Yanfeng Xu, Peter Pushko, Linlin Bao, Jing Yuan, Fengdi Li, Honglin Chen, Lili Xu, Qi Lv, Siu-Ying Lau, Chuan Qin
Rok vydání: 2016
Předmět:
0301 basic medicine
H5N1 vaccine
Hemagglutinin (influenza)
Hemagglutinin Glycoproteins
Influenza Virus
Biology
Influenza A Virus
H7N9 Subtype
medicine.disease_cause
Microbiology
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
Orthomyxoviridae Infections
Immunity
medicine
Animals
030212 general & internal medicine
Amino Acids
Lung
Mice
Inbred BALB C
Vaccines
Synthetic
Influenza A Virus
H5N1 Subtype
General Veterinary
General Immunology and Microbiology
Immunogenicity
Public Health
Environmental and Occupational Health
virus diseases
Hemagglutination Inhibition Tests
Virology
Reverse Genetics
Reverse genetics
Influenza A virus subtype H5N1
Titer
030104 developmental biology
Infectious Diseases
Influenza Vaccines
biology.protein
Receptors
Virus
Molecular Medicine
Female
Zdroj: Vaccine. 34:2627-2633
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2016.03.031
Popis: The continuous and sporadic human transmission of highly pathogenic avian H5N1 and H7N9 influenza viruses illustrates the urgent need for efficacious vaccines. However, all tested vaccines for the H5N1 and H7N9 viruses appear to be poorly immunogenic in mammals. In this study, a series of vaccines was produced using reverse genetic techniques that possess HA and NA genes from the H5N1 virus in the genetic background of the high-yield strain A/PR/8/34 (H1N1). Meanwhile, a group of H7N9 VLP vaccines that contain HA from H7N9 and NA and M1 from A/PR/8/34 (H1N1) was also produced. The HA amino acids of both the H5N1 and H7N9 vaccines differed at residues 226 and 228, both of which are critical for receptor specificity for an avian or mammalian host. Mice received two doses (3μg of HA each) of each vaccine and were challenged with lethal doses of wild type H5N1 or H7N9 viruses. The results showed that a recombinant H5N1 vaccine in which the HA amino acid G228 (avian specificity) was converted to S228 (mammalian specificity) resulted in higher HI titers, a lower viral titer in the lungs, and 100% protection in mice. However, a H7N9 VLP vaccine that contains L226 (mammalian specificity) and G228 (avian specificity) in HA showed better immunogenicity and protection efficacy in mice than VLP containing HA with either L226+S228 or Q226+S228. This observation indicated that specific HA residues could enhance a vaccine's protection efficacy and HA glycoproteins with both avian-type and human-type receptor specificities may produce better pandemic influenza vaccines for humans.
Databáze: OpenAIRE
Externí odkaz: