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Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice.
Vaccine. 2016 05 17; 34(23):2627-33.V

Abstract

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.

Authors+Show Affiliations

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Centre of Infection and Immunology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Centre of Infection and Immunology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.Medigen, 8420 Gas House Pike Suite S, Frederick, MD 21701, USA.State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Centre of Infection and Immunology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China. Electronic address: qinchuan@cnilas.org.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27083426

Citation

Xu, Lili, et al. "Hemagglutinin Amino Acids Related to Receptor Specificity Could Affect the Protection Efficacy of H5N1 and H7N9 Avian Influenza Virus Vaccines in Mice." Vaccine, vol. 34, no. 23, 2016, pp. 2627-33.
Xu L, Bao L, Lau SY, et al. Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice. Vaccine. 2016;34(23):2627-33.
Xu, L., Bao, L., Lau, S. Y., Wu, W. L., Yuan, J., Gu, S., Li, F., Lv, Q., Xu, Y., Pushko, P., Chen, H., & Qin, C. (2016). Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice. Vaccine, 34(23), 2627-33. https://doi.org/10.1016/j.vaccine.2016.03.031
Xu L, et al. Hemagglutinin Amino Acids Related to Receptor Specificity Could Affect the Protection Efficacy of H5N1 and H7N9 Avian Influenza Virus Vaccines in Mice. Vaccine. 2016 05 17;34(23):2627-33. PubMed PMID: 27083426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice. AU - Xu,Lili, AU - Bao,Linlin, AU - Lau,Siu-Ying, AU - Wu,Wai-Lan, AU - Yuan,Jing, AU - Gu,Songzhi, AU - Li,Fengdi, AU - Lv,Qi, AU - Xu,Yanfeng, AU - Pushko,Peter, AU - Chen,Honglin, AU - Qin,Chuan, Y1 - 2016/04/12/ PY - 2015/07/06/received PY - 2016/03/07/revised PY - 2016/03/14/accepted PY - 2016/4/17/entrez PY - 2016/4/17/pubmed PY - 2017/10/11/medline KW - Animal model KW - Influenza KW - Receptor specificity KW - Reverse genetics KW - Vaccine SP - 2627 EP - 33 JF - Vaccine JO - Vaccine VL - 34 IS - 23 N2 - 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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/27083426/Hemagglutinin_amino_acids_related_to_receptor_specificity_could_affect_the_protection_efficacy_of_H5N1_and_H7N9_avian_influenza_virus_vaccines_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(16)30004-4 DB - PRIME DP - Unbound Medicine ER -