The vaccinia‐based Sementis Copenhagen Vector coronavirus disease 2019 vaccine induces broad and durable cellular and humoral immune responses

• Published in: Immunology and cell biology 2022-04, Vol.100 (4), p.250-266
• Main Authors: Eldi, Preethi, Cooper, Tamara H, Prow, Natalie A, Liu, Liang, Heinemann, Gary K, Zhang, Voueleng J, Trinidad, Abigail D, Guzman‐Genuino, Ruth Marian, Wulff, Peter, Hobbs, Leanne M, Diener, Kerrilyn R, Hayball, John D
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; CD8 antigen; cellular responses; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Cytotoxicity; Humans; Immune response (humoral); Immunity, Cellular; Immunity, Humoral; Immunogenicity; Immunological memory; Lymphocytes T; Mice; Original; polyfunctional T cells; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; spike; Spike glycoprotein; Spike Glycoprotein, Coronavirus - genetics; Vaccination; vaccine; Vaccines; Vaccinia
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/imcb.12539

The ongoing coronavirus disease 2019 (COVID‐19) pandemic perpetuated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus‐based, replication‐defective Sementis Copenhagen Vector (SCV) was used to develop a first‐generation COVID‐19 vaccine encoding the spike glycoprotein (SCV‐S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust type 1 T helper‐biased, spike‐specific antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated that neutralizing antibody activity was maintained up to 9 months after vaccination in both young and middle‐aged mice, with durable immune memory evident even in the presence of pre‐existing vector immunity. Therefore, SCV‐S vaccination has a positive immunogenicity profile, with potential to expand protection generated by current vaccines in a heterologous boost format and presents a solid basis for second‐generation SCV‐based COVID‐19 vaccine candidates incorporating additional SARS‐CoV‐2 immunogens. In this study, we demonstrate that a nonreplicating vaccinia‐based viral vector expressing full‐length SARS‐CoV‐2 spike protein can rapidly generate spike‐specific polyfunctional T‐cell and antibody responses in young and middle‐aged, inbred and outbred strains of mice. Durable immune memory and neutralizing antibody activity were maintained for up to 9 months following a prime‐boost vaccination strategy.