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J. Vet. Sci. 2017; 18(S1): 299-306  
Optimized clade 2.3.2.1c H5N1 recombinant-vaccine strains against highly pathogenic avian influenza
Jin-Wook Jang1,3, Chung-Young Lee1,3, Il-hwan Kim4, Jun-Gu Choi5, Youn-Jeong Lee6, Seong-Su Yuk7, Ji-Ho Lee7, Chang-Seon Song7, Jae-Hong Kim1,3, Hyuk-Joon Kwon2,3,*
1Laboratory of Avian Diseases, 2Laboratory of Poultry Production Medicine, and 3College of Veterinary Medicine and BK21 PLUS for Veterinary Science, Seoul National University, Seoul 88026, Korea
4Center for Infectious Diseases, Korean National Institute of Health, Osong 28159, Korea
5Laboratory of Foreign Animal Disease and 6Laboratory of Avian Diseases, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea
7Laboratory of Avian Diseases, College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
Correspondence to: Tel: +82-2-880-1226; Fax: +82-2-885-6614; E-mail: kwonhj01@snu.ac.kr
Received: April 14, 2017; Revised: July 6, 2017; Accepted: July 14, 2017; Published online: August 31, 2017.
Abstract
A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice. In this study, we generated PR8-derived H5N1 recombinant viruses harboring hemagglutinin (attenuated) and neuraminidase genes of a clade 2.3.2.1c H5N1 HPAIV (K10-483), as well as the 01310 or 0028 PB2 genes, and investigated their replication and immunogenicity. Compared with a control virus harboring six internal PR8 genes (rK10-483), the recombinant viruses possessing the 01310 and 0028 PB2 genes showed significantly higher replication efficiency in ECEs and higher antibody titers in chickens. In contrast to rK10-483, none of the viruses replicated in BALB/c mice, and all showed low titers in Madin-Darby canine kidney cells. Additionally, the recombinant viruses did not induce a neutralization antibody but elicited decreased protective immune responses against K10-483 in mice. Thus, the highly replicative and mammalian nonpathogenic recombinant H5N1 strains might be promising vaccine candidates against HPAI in poultry.
Keywords: influenza A virus H5N1 subtype, polymerase basic 2 gene, reverse genetics, vaccines, virulence


© 2017 The Korean Society of Veterinary Science.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.