Preclinical proof of concept of a tetravalent lentiviral T-cell vaccine against dengue viruses

Frontiers in Immunology

Immunology

Philippe Souque¹  Amandine Noirat¹  Kirill Nemirov¹  Laleh Majlessi¹  Pierre Charneau¹  Pierre Authié¹  Catherine Blanc¹  Maryline Bourgine¹  Fanny Moncoq¹ 

[1] Pasteur-TheraVectys Joint Lab, Institut Pasteur, Université de Paris, Virology Department, Paris, France;

关键词: dengue;    DENV;    flavivirus;    lentiviral vector;    ifnar-/-mice;    tetravalent vaccine;    T-cell vaccine;    CD8+ T-cells;   

DOI  :  10.3389/fimmu.2023.1208041

 received in 2023-04-18, accepted in 2023-07-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

Dengue virus (DENV) is responsible for approximately 100 million cases of dengue fever annually, including severe forms such as hemorrhagic dengue and dengue shock syndrome. Despite intensive vaccine research and development spanning several decades, a universally accepted and approved vaccine against dengue fever has not yet been developed. The major challenge associated with the development of such a vaccine is that it should induce simultaneous and equal protection against the four DENV serotypes, because past infection with one serotype may greatly increase the severity of secondary infection with a distinct serotype, a phenomenon known as antibody-dependent enhancement (ADE). Using a lentiviral vector platform that is particularly suitable for the induction of cellular immune responses, we designed a tetravalent T-cell vaccine candidate against DENV (“LV-DEN”). This vaccine candidate has a strong CD8+ T-cell immunogenicity against the targeted non-structural DENV proteins, without inducing antibody response against surface antigens. Evaluation of its protective potential in the preclinical flavivirus infection model, i.e., mice knockout for the receptor to the type I IFN, demonstrated its significant protective effect against four distinct DENV serotypes, based on reduced weight loss, viremia, and viral loads in peripheral organs of the challenged mice. These results provide proof of concept for the use of lentiviral vectors for the development of efficient polyvalent T-cell vaccine candidates against all DENV serotypes.

【 授权许可】

Unknown   
Copyright © 2023 Nemirov, Authié, Souque, Moncoq, Noirat, Blanc, Bourgine, Majlessi and Charneau