Author: Collins, Katharine A ; Montoya-Díaz, Eduardo ; Janse, Chris J ; Lall, Amar ; González-Cerón, Lilia ; Reis, Fernando ; Hill, Adrian V S ; West, Heather ; Lopez-Camacho, Cesar ; Bauza, Karolis ; Khan, Shahid M ; Salman, Ahmed M ; Atcheson, Erwan ; Ramesar, Jai ; Reyes-Sandoval, Arturo ; Brod, Florian ; Pappas, Leontios

AbstractDevelopment of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation.

Frontiers in Immunology

An mRNA vaccine against rabies provides strong and durable protection in mice

Article

Author: Yue, Guangzhi ; Shi, Leitai ; Wang, Hongyu ; Cao, Shouchun ; Li, Jia ; Li, Yuhua ; Li, Miao ; Wu, Xiaohong ; Liu, Jingjing ; Huang, Yanqiu ; Li, Xingxing ; Fang, Enyue ; Liu, Xiaohui ; Xu, Hongshan ; Yang, Ren ; Zhao, Danhua ; Suo, Yue ; Liu, Xinyu ; Wang, Yunpeng ; Peng, Qinhua

IntroductionRabies is a serious public health problem worldwide for which an effective treatment method is lacking but can be prevented by vaccines. Current vaccines are produced in cell or egg cultures, which are both costly and time consuming.MethodsHere, a non-replicating mRNA vaccine (RV021) encoding the rabies virus glycoprotein was developed in vitro, and its immunogenicity and protective efficacy against live virus was evaluated in mice.ResultsA two-dose vaccination with 1 μg of RV021 at 7-day intervals induced a protective level of neutralizing antibody that was maintained for at least 260 days. RV021 induced a robust cellular immune response that was significantly superior to that of an inactivated vaccine. Two doses of 1 μg RV021 provided full protection against challenge with CVS of 30~60-fold lethal dose, 50%. Vaccine potency testing (according to the National Institutes of Health) in vivo revealed that the potency of RV021 at 15 μg/dose was 7.5 IU/dose, which is substantially higher than the standard for lot release of rabies vaccines for current human use.ConclusionThe mRNA vaccine RV021 induces a strong protective immune response in mice, providing a new and promising strategy for human rabies prevention and control.

100 Deals associated with RVL-021

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Indication	Highest Phase	Country/Location	Organization	Date
Okur-Chung neurodevelopmental syndrome	Preclinical	US	Unravel Biosciences, Inc.Startup	21 Sep 2023
Sleep Initiation and Maintenance Disorders	Preclinical	US	Unravel Biosciences, Inc.Startup	21 Sep 2023

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