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An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs.

ABSTRACT: Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capacity in mice and dogs. LVRNA001 induced neutralizing antibody production and a strong Th1 cellular immune response in mice. In both mice and dogs, LVRNA001 provided protection against challenge with 50-fold lethal dose 50 (LD₅₀) of RABV. With regards to protective efficiency, an extended dosing interval (14 days) induced greater antibody production than 3- or 7-day intervals in mice. Finally, post-exposure immunization against RABV was performed to evaluate the survival rates of dogs receiving two 25 μg doses of LVRNA001 vs. five doses of inactivated vaccine over the course of three months. Survival rate in the LVRNA001 group was 100%, whereas survival rate in the inactivated vaccine control group was only 33.33%. In conclusion, these results demonstrated that LVRNA001 induced strong protective immune responses in mice and dogs, which provides a new and promising prophylactic strategy for rabies.

SUBMITTER: Li J

PROVIDER: S-EPMC9652961 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs.

Li Jianglong J Liu Qi Q Liu Jun J Wu Xiaohong X Lei Yixin Y Li Shuang S Zhao Danhua D Li Zhi Z Luo Liping L Peng Sophia S Ou Yingrao Y Yang Hong H Jin Jing J Li Yuhua Y Peng Yucai Y

Virology journal 20221112 1

Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capac ...[more]

PMID: 36371169

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Project description:During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p < 0.01) dogs that received ORV or 21/27 (77.8%) as measured by ELISA (>40% blocking, p < 0.05). The fate of 291 oral vaccines was recorded; 283 dogs (97.2%) consumed the bait; 272 dogs (93.4%) were observed to puncture the blister, and only 14 blisters (4.8%) could not be retrieved by vaccinators and were potentially left in the environment. Pre-vaccination antibodies (RFFIT >0.05 IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community.

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An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs.

Publications

An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs.

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