Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses
•vHVT-H5 vaccines were tested for protection against HPAI viruses in chickens.•All vaccines provided clinical protection and reduced viral shedding.•COBRA vHVT-H5 vaccines elicited broadest antibody responses against diverse strains.•Wild-type vHVT-H5 vaccines elicited responses only against close g...
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| Veröffentlicht in: | Vaccine 2021-04, Vol.39 (14), p.1933-1942 |
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| creator | Bertran, Kateri Kassa, Aemro Criado, Miria F. Nuñez, Ivette A. Lee, Dong-Hun Killmaster, Lindsay Sá e Silva, Mariana Ross, Ted M. Mebatsion, Teshome Pritchard, Nikki Swayne, David E. |
| description | •vHVT-H5 vaccines were tested for protection against HPAI viruses in chickens.•All vaccines provided clinical protection and reduced viral shedding.•COBRA vHVT-H5 vaccines elicited broadest antibody responses against diverse strains.•Wild-type vHVT-H5 vaccines elicited responses only against close genetic clades.•Coupling recombinant HVT and COBRA holds promise for universal H5 poultry vaccines.
The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants. |
| doi_str_mv | 10.1016/j.vaccine.2021.02.075 |
| format | Article |
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The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2021.02.075</identifier><identifier>PMID: 33715903</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Antibodies ; Antigenic drift ; antigenic variation ; Antigens ; Aquatic birds ; Avian flu ; Avian influenza ; Birds ; China ; COBRA ; cross reaction ; Cytomegalovirus ; Drift ; Genetic engineering ; Hemagglutinins ; Homology ; HPAIV ; HVT recombinant vector vaccine ; Influenza ; Influenza A ; Inserts ; Marek's disease ; Pathogenicity ; Pathogens ; Phylogeny ; Poultry ; Reduction ; Strains (organisms) ; Vaccines ; Viruses</subject><ispartof>Vaccine, 2021-04, Vol.39 (14), p.1933-1942</ispartof><rights>2021</rights><rights>Published by Elsevier Ltd.</rights><rights>Copyright Elsevier Limited Apr 1, 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-3614246e905cf8825e586b6d2e62a86958f775762921399fcc4d2ac9a9a2f0873</citedby><cites>FETCH-LOGICAL-c473t-3614246e905cf8825e586b6d2e62a86958f775762921399fcc4d2ac9a9a2f0873</cites><orcidid>0000-0001-7472-1992 ; 0000-0003-1947-7469 ; 0000-0002-6920-4154</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X21002668$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33715903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bertran, Kateri</creatorcontrib><creatorcontrib>Kassa, Aemro</creatorcontrib><creatorcontrib>Criado, Miria F.</creatorcontrib><creatorcontrib>Nuñez, Ivette A.</creatorcontrib><creatorcontrib>Lee, Dong-Hun</creatorcontrib><creatorcontrib>Killmaster, Lindsay</creatorcontrib><creatorcontrib>Sá e Silva, Mariana</creatorcontrib><creatorcontrib>Ross, Ted M.</creatorcontrib><creatorcontrib>Mebatsion, Teshome</creatorcontrib><creatorcontrib>Pritchard, Nikki</creatorcontrib><creatorcontrib>Swayne, David E.</creatorcontrib><title>Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•vHVT-H5 vaccines were tested for protection against HPAI viruses in chickens.•All vaccines provided clinical protection and reduced viral shedding.•COBRA vHVT-H5 vaccines elicited broadest antibody responses against diverse strains.•Wild-type vHVT-H5 vaccines elicited responses only against close genetic clades.•Coupling recombinant HVT and COBRA holds promise for universal H5 poultry vaccines.
The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.</description><subject>Antibodies</subject><subject>Antigenic drift</subject><subject>antigenic variation</subject><subject>Antigens</subject><subject>Aquatic birds</subject><subject>Avian flu</subject><subject>Avian influenza</subject><subject>Birds</subject><subject>China</subject><subject>COBRA</subject><subject>cross reaction</subject><subject>Cytomegalovirus</subject><subject>Drift</subject><subject>Genetic engineering</subject><subject>Hemagglutinins</subject><subject>Homology</subject><subject>HPAIV</subject><subject>HVT recombinant vector vaccine</subject><subject>Influenza</subject><subject>Influenza A</subject><subject>Inserts</subject><subject>Marek's disease</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Phylogeny</subject><subject>Poultry</subject><subject>Reduction</subject><subject>Strains 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of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses</title><author>Bertran, Kateri ; Kassa, Aemro ; Criado, Miria F. ; Nuñez, Ivette A. ; Lee, Dong-Hun ; Killmaster, Lindsay ; Sá e Silva, Mariana ; Ross, Ted M. ; Mebatsion, Teshome ; Pritchard, Nikki ; Swayne, David E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-3614246e905cf8825e586b6d2e62a86958f775762921399fcc4d2ac9a9a2f0873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Antigenic drift</topic><topic>antigenic variation</topic><topic>Antigens</topic><topic>Aquatic birds</topic><topic>Avian flu</topic><topic>Avian influenza</topic><topic>Birds</topic><topic>China</topic><topic>COBRA</topic><topic>cross reaction</topic><topic>Cytomegalovirus</topic><topic>Drift</topic><topic>Genetic engineering</topic><topic>Hemagglutinins</topic><topic>Homology</topic><topic>HPAIV</topic><topic>HVT recombinant vector vaccine</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Inserts</topic><topic>Marek's disease</topic><topic>Pathogenicity</topic><topic>Pathogens</topic><topic>Phylogeny</topic><topic>Poultry</topic><topic>Reduction</topic><topic>Strains (organisms)</topic><topic>Vaccines</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bertran, Kateri</creatorcontrib><creatorcontrib>Kassa, Aemro</creatorcontrib><creatorcontrib>Criado, Miria F.</creatorcontrib><creatorcontrib>Nuñez, Ivette A.</creatorcontrib><creatorcontrib>Lee, Dong-Hun</creatorcontrib><creatorcontrib>Killmaster, Lindsay</creatorcontrib><creatorcontrib>Sá e Silva, Mariana</creatorcontrib><creatorcontrib>Ross, Ted 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Ivette A.</au><au>Lee, Dong-Hun</au><au>Killmaster, Lindsay</au><au>Sá e Silva, Mariana</au><au>Ross, Ted M.</au><au>Mebatsion, Teshome</au><au>Pritchard, Nikki</au><au>Swayne, David E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>39</volume><issue>14</issue><spage>1933</spage><epage>1942</epage><pages>1933-1942</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•vHVT-H5 vaccines were tested for protection against HPAI viruses in chickens.•All vaccines provided clinical protection and reduced viral shedding.•COBRA vHVT-H5 vaccines elicited broadest antibody responses against diverse strains.•Wild-type vHVT-H5 vaccines elicited responses only against close genetic clades.•Coupling recombinant HVT and COBRA holds promise for universal H5 poultry vaccines.
The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>33715903</pmid><doi>10.1016/j.vaccine.2021.02.075</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7472-1992</orcidid><orcidid>https://orcid.org/0000-0003-1947-7469</orcidid><orcidid>https://orcid.org/0000-0002-6920-4154</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elsevier ScienceDirect Journals Complete |
| subjects | Antibodies Antigenic drift antigenic variation Antigens Aquatic birds Avian flu Avian influenza Birds China COBRA cross reaction Cytomegalovirus Drift Genetic engineering Hemagglutinins Homology HPAIV HVT recombinant vector vaccine Influenza Influenza A Inserts Marek's disease Pathogenicity Pathogens Phylogeny Poultry Reduction Strains (organisms) Vaccines Viruses |
| title | Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses |
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