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

被引:9
作者
Bertran, Kateri [1 ,7 ]
Kassa, Aemro [2 ]
Criado, Miria F. [1 ,3 ]
Nunez, Ivette A. [3 ]
Lee, Dong-Hun [4 ]
Killmaster, Lindsay [1 ]
Silva, Mariana Sa e [2 ]
Ross, Ted M. [3 ,5 ]
Mebatsion, Teshome [2 ]
Pritchard, Nikki [6 ]
Swayne, David E. [1 ]
机构
[1] ARS, Exot & Emerging Avian Viral Dis Res Unit, Southeast Poultry Res Lab, US Natl Poultry Res Ctr,USDA, 934 Coll Stn Rd, Athens, GA 30605 USA
[2] Boehringer Ingelheim Anim Hlth USA Inc, 1730 Olymp Dr, Athens, GA 30601 USA
[3] Univ Georgia, Ctr Vaccines & Immunol, Athens, GA 30602 USA
[4] Univ Connecticut, Dept Pathobiol & Vet Sci, Storrs, CT 06269 USA
[5] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA
[6] Boehringer Ingelheim Anim Hlth USA Inc, 1112 Airport Pkwy, Gainesville, GA 30503 USA
[7] IRTA UAB, IRTA, Ctr Recerca Sanitat Anim CReSA, Campus UAB, Bellaterra 08193, Spain
关键词
HPAIV; Avian influenza; HVT recombinant vector vaccine; COBRA; H5;
D O I
10.1016/j.vaccine.2021.02.075
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. Published by Elsevier Ltd.
引用
收藏
页码:1933 / 1942
页数:10
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