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Title:   Author  item
                                            Kapczynski, Darrellitem
                                            TUMPEY, TERRENCE - Centers For Disease Control And Prevention (CDC) - United Statesitem
                                            HIDAJAT, RACHMAT - Medigen, Incitem
                                            Zsak, Anikoitem
                                            CHRZASTEK, KLAUDIA - Orise Fellowitem
                                            TRETYAKOVA, IRINA - Medigen, Incitem
                                            PUSHKO, PETER - Medigen, Inc
  Submitted to: Vaccine
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/1/2016
                                    Publication  Date: 3/18/2016
                                    Publication URL: https://handle.nal.usda.gov/10113/62787Citation: Kapczynski, D.R., Tumpey, T.M., Hidajat, R., Zsak, A., Chrzastek, K., Tretyakova, I., Pushko, P. 2016. Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses. Vaccine. 34(13):1575-1581. doi:10.1016/j.vaccine.2016.02.011.Interpretive Summary: Avian influenza (AI) is a highly contagious, agriculturally–relevant disease that can severely affect the poultry industry and the national food supply and safety.  The AI virus also represents an acute threat to public health.  The viruses vary widely in their pathogenicity and the ability to cause disease among birds.  The viruses are divided into low-pathogenic AI (LPAI) and highly pathogenic AI (HPAI) strains. HPAI viruses, especially H5 subtype strains, cause widespread morbidity and mortality in domestic bird populations.  Furthermore, with an increasing number of human infections of HPAI of the H5 subtype, there is a growing concern that this virus could cause a pandemic.  One strategy to control AI, including H5 HPAI, is the development of effective vaccines for use in the poultry industry.  In the current study, we prepared novel recombinant virus-like particles (VLPs) as vaccine to protect against AI viruses of H5 subtype.  Following vaccination of birds with VLPs, complete protection against three H5 HPAI viruses was demonstrated.  Our research demonstrates that H5 VLPs is a promising candidate for a safe and highly immunogenic vaccine against AI.
                                Technical 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.


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