Immunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheep

Autor: Gregory M. Jacobson, Kirsty Kraakman, Olivia Wallace, Jolyn Pan, Alex Hennebry, Grant Smolenski, Ray Cursons, Steve Hodgkinson, Adele Williamson, William Kelton
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Biotechnology Reports, Vol 38, Iss , Pp e00791- (2023)
Druh dokumentu: article
ISSN: 2215-017X
DOI: 10.1016/j.btre.2023.e00791
Popis: Antigen-specific polyclonal immunoglobulins derived from the serum, colostrum, or milk of immunized ruminant animals have potential as scalable therapeutics for the control of viral diseases including COVID-19. Here we show that the immunization of sheep with fusions of the SARS-CoV-2 receptor binding domain (RBD) to ovine IgG2a Fc domains promotes significantly higher levels of antigen-specific antibodies compared to native RBD or full-length spike antigens. This antibody population contained elevated levels of neutralizing antibodies that suppressed binding between the RBD and hACE2 receptors in vitro. A second immune-stimulating fusion candidate, Granulocyte-macrophage colony-stimulating factor (GM-CSF), induced high neutralizing responses in select animals but narrowly missed achieving significance. We further demonstrated that the antibodies induced by these fusion antigens were transferred into colostrum/milk and possessed cross-neutralizing activity against diverse SARS-CoV-2 variants. Our findings highlight a new pathway for recombinant antigen design in ruminant animals with applications in immune milk production and animal health.
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