A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains
| Autor: | Kateri Bertran, Tod Strugnell, Ted M. Ross, Joshua M. DiNapoli, Harry Kleanthous, Chalise E. Bloom, Maryann Giel-Moloney, David E. Swayne, Michel Bublot, Teshome Mebatsion, Mariana Sá e Silva, Charles L. Balzli |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Influenza vaccine
030231 tropical medicine Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus medicine.disease_cause complex mixtures Virus 03 medical and health sciences 0302 clinical medicine Goose Antigen biology.animal Influenza Human medicine Animals Humans Vaccines Virus-Like Particle 030212 general & internal medicine Antigens Viral Phylogeny Hemagglutination assay Influenza A Virus H5N1 Subtype General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health virus diseases Antigenic Variation Virology Influenza A virus subtype H5N1 Vaccinology Titer Infectious Diseases Influenza Vaccines Influenza in Birds biology.protein Molecular Medicine Chickens |
| Zdroj: | Vaccine. 37:2369-2376 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2019.03.018 |
| Popis: | Since the first identification of the H5N1 Goose/Guangdong lineage in 1996, this highly pathogenic avian influenza virus has spread worldwide, becoming endemic in domestic poultry. Sporadic transmission to humans has raised concerns of a potential pandemic and underscores the need for a broad cross-protective influenza vaccine. Here, we tested our previously described methodology, termed Computationally Optimized Broadly Reactive Antigen (COBRA), to generate a novel hemagglutinin (HA) gene, termed COBRA-2, that was based on H5 HA sequences from 2005 to 2006. The COBRA-2 HA virus-like particle (VLP) vaccines were used to vaccinate chickens and the immune responses were compared to responses elicited by VLP's expressing HA from A/whooper swan/Mongolia/244/2005 (WS/05), a representative 2005 vaccine virus from clade 2.2. To support this evaluation a hemagglutination inhibition (HAI) breadth panel was developed consisting of phylogenetically and antigenically diverse H5 strains in circulation from 2005 to 2006, as well as recent drift variants (2008 - 2014). We found that the COBRA-2 VLP vaccines elicited robust HAI titers against this entire breadth panel, whereas the VLP vaccine based upon the recommended WS/05 HA only elicited HAI responses against a subset of strains. Furthermore, while all vaccines protected chickens against challenge with the WS/05 virus, only the human COBRA-2 VLP vaccinated birds were protected (80%) against a recent drifted clade 2.3.2.1B, A/duck/Vietnam/NCVD-672/2011 (VN/11) virus. This is the first report to demonstrate seroprotective antibody responses against genetically diverse clades and sub-clades of H5 viruses and protective efficacy against a recent drifted variant using a globular head based design strategy. |
| Databáze: | OpenAIRE |
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