Vetnews | September 2024 20 « BACK TO CONTENTS these tissues decreased, and it was still detected on day 60 Overall, the animals showed good tolerance to the RG SAM (CNE) vaccine, which triggered the expected IgG immune response. Since 2020, there has been a surge of interest in mRNA rabies vaccine research, driven by interest in mRNA COVID-19 vaccines. In 2022, Lavida developed a non-replicating mRNA rabies vaccine LVRNA001 based on the Therapeutics platform (Chinese patent ZL201911042634.2).80 The ORF of the vaccine mRNA encodes the glycoprotein (RABV-G) of the CTN-1 strain (GenBank: ARC39382.1), which has been used to produce human rabies vaccines in China,89,90 The vaccine uses LNPs as a delivery system. The results showed that LVRNA001 can induce sustained neutralizing antibodies and strong Th1 cell immune responses in mice and maintain high antibody levels for at least 6 months after immunization. The induced antibodies can effectively prevent the replication of the virus in mice and dogs, and have a protective effect against challenge with 50LD50 RABV. Compared to a 3-day or 7-day dosing interval, extending the dosing interval in mice (14 days) can produce more antibodies. In addition, the immune protective effect in dogs after exposure showed that the survival rate after two doses of LVRNA001 was 100%, while the three-month survival rate of the inactivated vaccine control group was only 33.33%. LVRNA001 induces strong protective immune responses in both mice and dogs. To explore the impact of the administration route on the efficacy of RNA vaccines, Anderluzzi et al.81 investigated the immunogenicity of self-amplifying mRNA encoding RABVG on different nanoparticle platforms (solid lipid nanoparticles, polymer nanoparticles, and lipid nanoparticles). The results indicated that among the four nanoparticle formulations, intramuscular and intradermal injections initially showed similar immunogenicity, but ionizable lipid nanoparticles exhibited higher long-term IgG responses. However, intranasal administration can lead to a lower immune response and rapid clearance, regardless of the formula used. This indicates that both the route of administration and the form of nanoparticles can affect the efficacy of saRNA vaccines. By 2023, there were numerous preclinical studies on mRNA rabies vaccines. For example, a non-replicating mRNA vaccine (SYS6008)82 encoding the RABV (CTN-1 strain) RABV-G and tested its immunogenicity and immune protection in mice, as well as its immunogenicity and immune persistence in cynomolgus macaques. SYS6008 stimulated mice to produce higher levels of RVNA faster than the Rabipur-inactivated vaccine. In a PrEP mouse model, intramuscular injection with a 1/30 human dose of SYS6008 alone was able to resist the attack of a lethal dose of RABV. In the PEP model, the immunoprotective effect of SYS6008 was greater than that of the control vaccine. In addition, SYS6008 can generate a good immune response in cynomolgus macaques, and RVNA levels can be maintained at effective levels in Table 2. Preclinical trials. Year Vaccine Platform Vaccine Forms Delivery Platform Preclinical Setting Ref. 2009 Division of Animal Biotechnology, Indian Veterinary Research Institute Sin-Rab -G-RNA self- amplifying Mrna / mice 78 2016 CureVac RABV-G mRNA non- amplifying mRNA Protamin mice and pigs 61 2020 GSK RG SAM (NEG) self- amplifying mRNA Cationic nanoemulsion rats 62 2022 Liverna LVRNA001 non- replicating mRNA LNPs mice and dogs 79 2022 GSK RVG-saRNA self- amplifying mRNA SLNs; PNPs; LNPs mice 82 2023 CSPC SYS6008 non- replicating mRNA LNPs mice and cynomolgus macaques 83 2023 AMMS mRNA- B-LNP / LNPs mice and dogs 84 2023 Fudan University RABV-G mRNA-LNP non- amplifying mRNA LNPs mice 85 2023 Karolinska Institutet RABV-G mRNA / LNPs Chinese rhesus macaques 86 2023 Chengdu Qingbaijiang District People’s Hospital RABV G mRNA non- amplifying mRNA LNP and nucleic acid immunostimulator (CPG 1018, CPG 2395 and Poly I:C) mice 87 2023 Vaccines R&D Department, Changchun Institute of Biological Products RV021 non- amplifying mRNA LNPs mice 88 2023 Huazhong Agricultural University LPP-mRNA -G non- amplifying mRNA LPP mice and dogs 89 Development of mRNA rabies vaccines <<<19
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