title: Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses.
abstract: Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co-expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus.
authors: USDA SEPRL, Athens, GA, USA.
authors: Darrell R
authors: DR
authors: Kapczynski
authors: Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA, USA.
authors: Terrence M
authors: TM
authors: Tumpey
authors: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA.
authors: Rachmat
authors: R
authors: Hidajat
authors: USDA SEPRL, Athens, GA, USA.
authors: Aniko
authors: A
authors: Zsak
authors: USDA SEPRL, Athens, GA, USA.
authors: Klaudia
authors: K
authors: Chrzastek
authors: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA.
authors: Irina
authors: I
authors: Tretyakova
authors: Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD, USA. Electronic address: ppushko@medigen-usa.com.
authors: Peter
authors: P
authors: Pushko
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016367:Baculoviridae; D002645:Chickens; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000517:prevention & control*; D014611:Vaccination / Q000662:veterinary*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: Avian influenza; Trivalent; VLP vaccine; Virus-like particle