PMID- 32783766 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 2164-554X (Electronic) IS - 2164-5515 (Print) IS - 2164-5515 (Linking) VI - 16 IP - 9 DP - 2020 Sep 1 TI - Immune-engineered H7N9 influenza hemagglutinin improves protection against viral influenza virus challenge. PG - 2042-2050 LID - 10.1080/21645515.2020.1793711 [doi] AB - The influenza hemagglutinin (HA) isolated from avian H7N9 influenza virus strains elicit weak immune responses. This low immunogenicity may be due to a regulatory T cell (T(reg))-stimulating epitopes in HA from the H7N9 isolate A/Anhui/1/2013 (Anh/13). In this report, this T(reg) stimulating sequence was removed from the wild-type (WT) H7 HA amino acid sequence and replaced with a conserved CD4 + T cell stimulating sequences from human seasonal H3N2 strains and designed OPT1 H7 HA. The effectiveness of this optimized H7 HA protein was determined using a humanized mouse (HLA-DR3) expressing the human leukocyte antigen (HLA) DR3 allele. HLA-DR3 mice were pre-immunized by infecting with H3N2 influenza virus, A/Hong Kong/4108/2014 and then vaccinated intramuscularly with either the WT H7 HA from Anh/13 or the OPT1 H7 HA antigen without adjuvant. The OPT1 H7 HA vaccination group elicited higher H7 HA-specific IgG titers that resulted in a lower mortality, weight loss, and lung viral titer following lethal challenge with the H7N9 Anh/13 influenza virus compared to WT-vaccinated mice. Overall, T-cell epitope-engineered vaccines can improve the immunogenicity of H7 HA antigens resulting in enhanced survival and lower morbidity against H7N9 influenza virus challenge. FAU - Jang, Hyesun AU - Jang H AD - Department of Infectious Diseases, University of Georgia , Athens, GA, USA. AD - Center for Vaccines and Immunology, University of Georgia , Athens, GA, USA. FAU - Meyers, Lauren M AU - Meyers LM AD - EpiVax , Providence, RI, USA. FAU - Boyle, Christine AU - Boyle C AD - EpiVax , Providence, RI, USA. FAU - De Groot, Anne S AU - De Groot AS AD - Center for Vaccines and Immunology, University of Georgia , Athens, GA, USA. AD - EpiVax , Providence, RI, USA. FAU - Moise, Lenny AU - Moise L AD - EpiVax , Providence, RI, USA. AD - Institute of Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island , Providence, RI, USA. FAU - Ross, Ted M AU - Ross TM AD - Department of Infectious Diseases, University of Georgia , Athens, GA, USA. AD - Center for Vaccines and Immunology, University of Georgia , Athens, GA, USA. LA - eng GR - R01 AI132205/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200812 PL - United States TA - Hum Vaccin Immunother JT - Human vaccines & immunotherapeutics JID - 101572652 RN - 0 (Antibodies, Viral) RN - 0 (Hemagglutinin Glycoproteins, Influenza Virus) RN - 0 (Hemagglutinins) RN - 0 (Influenza Vaccines) SB - IM MH - Animals MH - Antibodies, Viral MH - Hemagglutinin Glycoproteins, Influenza Virus/genetics MH - Hemagglutinins MH - Influenza A Virus, H3N2 Subtype MH - *Influenza A Virus, H7N9 Subtype/genetics MH - *Influenza Vaccines MH - *Influenza, Human/prevention & control MH - Mice MH - *Orthomyxoviridae Infections/prevention & control PMC - PMC7553694 OTO - NOTNLM OT - Asian H7N9 OT - T cell epitope engineering OT - humanized mouse model OT - pandemic influenza vaccine EDAT- 2020/08/14 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/08/12 CRDT- 2020/08/14 06:00 PHST- 2020/08/14 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/08/14 06:00 [entrez] PHST- 2020/08/12 00:00 [pmc-release] AID - 1793711 [pii] AID - 10.1080/21645515.2020.1793711 [doi] PST - ppublish SO - Hum Vaccin Immunother. 2020 Sep 1;16(9):2042-2050. doi: 10.1080/21645515.2020.1793711. Epub 2020 Aug 12.