Development of in ovo-compatible NS1-truncated live attenuated influenza vaccines by modulation of hemagglutinin cleavage and polymerase acidic X frameshifting sites.

Autor: Ghorbani A; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA., Ngunjiri JM; Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA., Edward C Abundo M; Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA., Pantin-Jackwood M; Southeast Poultry Research Laboratory, US National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA, USA., Kenney SP; Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA. Electronic address: kenney.157@osu.edu., Lee CW; Southeast Poultry Research Laboratory, US National Poultry Research Center, Agricultural Research Service, U.S. Department of Agriculture, Athens, GA, USA. Electronic address: chang.lee@usda.gov.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2023 Mar 10; Vol. 41 (11), pp. 1848-1858. Date of Electronic Publication: 2023 Jan 18.
DOI: 10.1016/j.vaccine.2023.01.018
Abstrakt: Emerging avian influenza viruses pose a high risk to poultry production, necessitating the need for more broadly protective vaccines. Live attenuated influenza vaccines offer excellent protective efficacies but their use in poultry farms is discouraged due to safety concerns related to emergence of reassortant viruses. Vaccination of chicken embryos inside eggs (in ovo) induces early immunity in young chicks while reduces the safety concerns related to the use of live vaccines on farms. However, in ovo vaccination using influenza viruses severely affects the egg hatchability. We previously engineered a high interferon-inducing live attenuated influenza vaccine candidate with an enhanced protective efficacy in chickens. Here, we asked whether we could further modify this high interferon-inducing vaccine candidate to develop an in ovo-compatible live attenuated influenza vaccine. We first showed that the enhanced interferon responses induced by the vaccine is not enough to attenuate the virus in ovo. To reduce the pathogenicity of the virus for chicken embryos, we replaced the hemagglutinin cleavage site of the H7 vaccine virus (PENPKTR/GL) with that of the H6-subtype viruses (PQIETR/GL) and disrupted the ribosomal frameshifting site responsible for viral polymerase acidic X protein expression. In ovo vaccination of chickens with up to 10 5 median egg infectious dose of the modified vaccine had minimal effects on hatchability while protecting the chickens against a heterologous challenge virus at two weeks of age. This study demonstrates that targeted genetic mutations can be applied to further attenuate and enhance the safety of live attenuated influenza vaccines to develop future in ovo vaccines for poultry.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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