A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains. Issue 17 (17th April 2019)

• Record Type: Journal Article
• Authors: Ross, Ted M.; DiNapoli, Joshua; Giel-Moloney, Maryann; Bloom, Chalise E.; Bertran, Kateri; Balzli, Charles; Strugnell, Tod; Sá e Silva, Mariana; Mebatsion, Teshome; Bublot, Michel; Swayne, David E.; Kleanthous, Harry
• Is Part Of: Vaccine. Volume 37:Issue 17(2019)
• Page Start: 2369
• Page End: 2376
• Publication Date: 2019-04-17
• Subjects: Influenza -- H5N1 -- Universal vaccine -- Chickens -- COBRA -- Pre-pandemic; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.03.018
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Vaccination is the most effective strategy in pre-pandemic preparedness. Engineered HA immunogens can elicit protective immunity against drift variants. A computational design strategy could reduce frequent vaccine updates. Abstract: 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.