Single-Dose Dendritic Cell-Targeted COVID-19 Vaccine Shows Exceptional Durability and Protection in Mice<\/b><\/p>\n
Singapore & Melbourne, July 2024 \u2014 A groundbreaking study led by researchers from the Alonso group in the LSI Immunology Programme and Monash University has unveiled a promising next-generation COVID-19 vaccine that requires only a single dose to trigger long-lasting and broad immunity. The findings, published in Molecular Therapy, suggest that targeting vaccine candidates to a specific subset of dendritic cells could overcome critical limitations of existing COVID-19 vaccines. Current vaccines, while lifesaving, face challenges such as waning immunity, limited T cell responses, and poor protection at mucosal sites like the lungs. To address this, the team engineered a novel antibody-based construct, Clec9A-RBD, designed to deliver the SARS-CoV-2 receptor-binding domain (RBD) directly to conventional type 1 dendritic cells (cDC1). <\/p>\n
These cells are powerful antigen-presenters that orchestrate robust antibody and T cell responses. In mouse studies, a single systemic injection of Clec9A-RBD induced remarkably durable immunity. Antibody responses remained strong for up to 21 months, with evidence of affinity maturation \u2014 meaning antibodies improved in strength and breadth over time. Importantly, these antibodies displayed neutralizing and antibody-dependent cellular cytotoxicity (ADCC) activity not only against ancestral SARS-CoV-2 but also across variants of concerns including pre-Omicron and Omicron lineages, as well as other related coronaviruses from the bat and pangolin lineages. <\/p>\n
The vaccine also generated a sustained T cell response, including both CD4+ and CD8+ subsets. These responses were cross-reactive with all tested variants of concern, including Omicron subvariants, and a subset of polyfunctional T cells capable of producing multiple cytokines was detected. Notably, Clec9A-RBD stimulated significant mucosal immunity in the lungs, with tissue-resident memory T cells and protective antibodies present at respiratory surfaces. When vaccinated mice were challenged with ancestral SARS-CoV-2, they were fully protected, which correlated with significantly less weight loss and 100-fold lower viral loads in the lungs compared with unvaccinated controls. <\/p>\n
The findings therefore suggest that Clec9A-RBD single shot immunization is expected to trigger robust and sustained, systemic and mucosal protective immunity against rapidly evolving SARS-CoV2 variants. With scalable antibody-based manufacturing, the Clec9A-taregting vaccine platform offers a cost-effective and rapidly deployable solution for future pandemics. As the equivalent of cDC1 subset exists in humans, the clinical application of this vaccine strategy is a realistic and exciting avenue. <\/p>\n
Reference:
\nCheang NYZ, Tan KS, Tan PS, et al. Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice. Molecular Therapy. 2024. DOI: 10.1016\/j.ymthe.2024.05.003<\/p>\n","protected":false},"excerpt":{"rendered":"
Single-Dose Dendritic Cell-Targeted COVID-19 Vaccine Shows Exceptional Durability and Protection in Mice Singapore & Melbourne, July 2024 \u2014 A groundbreaking study led by researchers from the Alonso group in the LSI Immunology Programme and Monash University has unveiled a promising next-generation COVID-19 vaccine that requires only a single dose to trigger long-lasting and broad immunity.Read More<\/a><\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[36],"class_list":["post-2438","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-mm-immunology"],"_links":{"self":[{"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/posts\/2438"}],"collection":[{"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/comments?post=2438"}],"version-history":[{"count":2,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/posts\/2438\/revisions"}],"predecessor-version":[{"id":2452,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/posts\/2438\/revisions\/2452"}],"wp:attachment":[{"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/media?parent=2438"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/categories?post=2438"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.nus.edu.sg\/lsi\/wp-json\/wp\/v2\/tags?post=2438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}