NEWS
Two Doses! 100% Protection Rate! AIM mRNA Rabies Vaccine Induces Durable and Comprehensive Immune Response
The rabies vaccine market in China still holds significant growth potential, with rapid technological iteration and upgrades. Companies and research institutions, including AIM Vaccines and CureVac, have already developed novel mRNA rabies vaccines. Recently, a research team from China Pharmaceutical University published a study in the journal Molecular Therapy, indicating that mRNA vaccines can induce high-level virus-neutralizing antibodies (VNA), sustained humoral and cellular responses, and immunological memory in rhesus macaques at a low dose, with good safety. It can also provide full protection against lethal rabies virus attacks in mice.
Not long ago, AIM Vaccines/Li Fanda, in collaboration with the National Institute of Viral Disease Control and Prevention, published an evaluation of the protective efficacy and safety of their independently developed mRNA rabies candidate vaccine LVRNA001 across different animal models.
In preclinical studies by AIM Vaccines, the team first tested the protective efficacy of LVRNA001 in dogs. Dogs were vaccinated twice (D0-7 immunization schedule) with 10 μg or 50 μg LVRNA001 prior to challenge with a lethal dose of RABV. Dogs in the control group were vaccinated three times (D0-7-21 immunization schedule) with human-dose inactivated vaccine or PBS. All dogs were challenged with 50 times the LD50 (median lethal dose) of street virus strain BD06 on day 35.
The results showed a 100% survival rate in the high-dose and low-dose LVRNA001 and inactivated vaccine groups, while the survival rate in the PBS group was 0%. High levels of neutralizing antibodies, above the WHO-recommended protective threshold of 0.5 IU/mL, were detectable in all vaccinated groups on D7, D9, D11, D35, and D125. Most importantly, the LVRNA001-vaccinated group maintained higher neutralizing antibody titers on D125 compared to the inactivated vaccine group, indicating that LVRNA001 vaccination induces stronger and more durable immune protective response than inactivated vaccines.
Next, the vaccine efficacy after rabies virus exposure continued to be evaluated. Four groups of dogs were first infected via intramuscular injection with 50 times the LD50 virulence RABV-BD06 strain. Six hours after viral infection, dogs were vaccinated with LVRNA001 (10 or 50 μg, D0-7). Additionally, dogs received five human-doses of inactivated vaccine (D0-3-7-14-28) as a positive control, and PBS as a negative control. Ninety days after vaccination, the survival rate data showed that dogs vaccinated with two doses of 10 or 50 μg LVRNA001 and five doses of inactivated vaccine had a 100% survival rate, while all PBS-treated dogs died. Three months after post-exposure vaccination, the neutralizing antibody levels detected in the mRNA high/low dose groups were relatively higher compared to the inactivated vaccine group.
In mice, compared to inactivated vaccines administered in a five-dose regimen, two doses of LVRNA001 induced significantly higher levels of neutralizing antibodies. Notably, the high-dose LVRNA001 group achieved a 100% seroconversion rate in mice on day 5 after the first immunization and enabled mice to produce protective neutralizing antibodies above 0.5 IU/mL more rapidly. This indicates that LVRNA001 can stimulate mice to produce higher levels of neutralizing antibodies faster than inactivated vaccines, which is particularly important for severe post-exposure treatment, as it can more effectively intercept the virus before it reaches the central nervous system.
Subsequent pre-exposure immunization protection efficacy results in mice showed that a single dose of LVRNA001 provided 100% protection in mice challenged with the virus. Post-exposure administration of two doses of high-dose LVRNA001 under different immunization schedules (D0-7 or D0-14) provided ideal protection effect, with average protection rates of 85.71% and 88.57% against seven representative strains of rabies virus in China (China I-VII strains: SC16, GD1, NM3, QH2, LY, YN3, and XZ17. To distinguish the protection rates of different vaccines and immunization schedules, the challenge dose was set much higher than the conventional requirement to avoid a uniform 100% protection rate). In comparison, the protection rate of the high-dose inactivated vaccine group administered in a five-dose regimen was only 52.8%.
Studies have shown that repeated administration of LVRNA001 in crab-eating macaques, dogs, and rats does not cause systemic toxicity. It can effectively induce a strong specific immune response against the rabies virus while maintaining a relatively safe profile, indicating that LVRNA001 is a promising rabies vaccine candidate.
Previously, CureVac published a study in Nature Communications on the protective efficacy of mRNA rabies vaccines in rhesus macaque models and conducted a head-to-head comparison trial with the licensed inactivated vaccine Rabipur. Compared to Rabipur, the mRNA vaccine encoding RABV-G induced higher levels of cross-neutralizing antibodies and broader reactive antibody protection.
Analyses suggest that rabies virus (RABV) vaccines based on fully inactivated viruses have saved countless lives in the human fight against rabies. Although highly effective human rabies vaccines and immunoglobulins are available for post-exposure prophylaxis, they are not necessarily accessible or available in regions with high demand. Currently, the only approved type of rabies vaccine is inactivated, with limited immunogenicity. The World Health Organization recommends a three-dose immunization schedule for pre-exposure prophylaxis and four to five doses for post-exposure prophylaxis. These complex immunization schedules impose a significant burden on high-risk populations in low-income and remote areas.
Data show that the domestic rabies vaccine market is expected to grow to 10.1 billion yuan by 2026. With a large number of dogs, high mobility, and low registration and management rates nationwide, the task of rabies prevention and control remains challenging. Until the vaccination rate of veterinary rabies vaccines in China reaches a high level, post-exposure prophylaxis measures remain necessary after animal bites, indicating that the rabies vaccine market in China still holds significant growth potential.
mRNA vaccine production is rapid and cost-effective, with flexibility in antigen design, making it an important pathway for preventive vaccine development. Internationally, mRNA rabies vaccines under development have shown good protective effects and tolerability in existing studies.
Not long ago, AIM Vaccines/Li Fanda, in collaboration with the National Institute of Viral Disease Control and Prevention, published an evaluation of the protective efficacy and safety of their independently developed mRNA rabies candidate vaccine LVRNA001 across different animal models.
In preclinical studies by AIM Vaccines, the team first tested the protective efficacy of LVRNA001 in dogs. Dogs were vaccinated twice (D0-7 immunization schedule) with 10 μg or 50 μg LVRNA001 prior to challenge with a lethal dose of RABV. Dogs in the control group were vaccinated three times (D0-7-21 immunization schedule) with human-dose inactivated vaccine or PBS. All dogs were challenged with 50 times the LD50 (median lethal dose) of street virus strain BD06 on day 35.
The results showed a 100% survival rate in the high-dose and low-dose LVRNA001 and inactivated vaccine groups, while the survival rate in the PBS group was 0%. High levels of neutralizing antibodies, above the WHO-recommended protective threshold of 0.5 IU/mL, were detectable in all vaccinated groups on D7, D9, D11, D35, and D125. Most importantly, the LVRNA001-vaccinated group maintained higher neutralizing antibody titers on D125 compared to the inactivated vaccine group, indicating that LVRNA001 vaccination induces stronger and more durable immune protective response than inactivated vaccines.
Next, the vaccine efficacy after rabies virus exposure continued to be evaluated. Four groups of dogs were first infected via intramuscular injection with 50 times the LD50 virulence RABV-BD06 strain. Six hours after viral infection, dogs were vaccinated with LVRNA001 (10 or 50 μg, D0-7). Additionally, dogs received five human-doses of inactivated vaccine (D0-3-7-14-28) as a positive control, and PBS as a negative control. Ninety days after vaccination, the survival rate data showed that dogs vaccinated with two doses of 10 or 50 μg LVRNA001 and five doses of inactivated vaccine had a 100% survival rate, while all PBS-treated dogs died. Three months after post-exposure vaccination, the neutralizing antibody levels detected in the mRNA high/low dose groups were relatively higher compared to the inactivated vaccine group.
In mice, compared to inactivated vaccines administered in a five-dose regimen, two doses of LVRNA001 induced significantly higher levels of neutralizing antibodies. Notably, the high-dose LVRNA001 group achieved a 100% seroconversion rate in mice on day 5 after the first immunization and enabled mice to produce protective neutralizing antibodies above 0.5 IU/mL more rapidly. This indicates that LVRNA001 can stimulate mice to produce higher levels of neutralizing antibodies faster than inactivated vaccines, which is particularly important for severe post-exposure treatment, as it can more effectively intercept the virus before it reaches the central nervous system.
Subsequent pre-exposure immunization protection efficacy results in mice showed that a single dose of LVRNA001 provided 100% protection in mice challenged with the virus. Post-exposure administration of two doses of high-dose LVRNA001 under different immunization schedules (D0-7 or D0-14) provided ideal protection effect, with average protection rates of 85.71% and 88.57% against seven representative strains of rabies virus in China (China I-VII strains: SC16, GD1, NM3, QH2, LY, YN3, and XZ17. To distinguish the protection rates of different vaccines and immunization schedules, the challenge dose was set much higher than the conventional requirement to avoid a uniform 100% protection rate). In comparison, the protection rate of the high-dose inactivated vaccine group administered in a five-dose regimen was only 52.8%.
Studies have shown that repeated administration of LVRNA001 in crab-eating macaques, dogs, and rats does not cause systemic toxicity. It can effectively induce a strong specific immune response against the rabies virus while maintaining a relatively safe profile, indicating that LVRNA001 is a promising rabies vaccine candidate.
Previously, CureVac published a study in Nature Communications on the protective efficacy of mRNA rabies vaccines in rhesus macaque models and conducted a head-to-head comparison trial with the licensed inactivated vaccine Rabipur. Compared to Rabipur, the mRNA vaccine encoding RABV-G induced higher levels of cross-neutralizing antibodies and broader reactive antibody protection.
Analyses suggest that rabies virus (RABV) vaccines based on fully inactivated viruses have saved countless lives in the human fight against rabies. Although highly effective human rabies vaccines and immunoglobulins are available for post-exposure prophylaxis, they are not necessarily accessible or available in regions with high demand. Currently, the only approved type of rabies vaccine is inactivated, with limited immunogenicity. The World Health Organization recommends a three-dose immunization schedule for pre-exposure prophylaxis and four to five doses for post-exposure prophylaxis. These complex immunization schedules impose a significant burden on high-risk populations in low-income and remote areas.
Data show that the domestic rabies vaccine market is expected to grow to 10.1 billion yuan by 2026. With a large number of dogs, high mobility, and low registration and management rates nationwide, the task of rabies prevention and control remains challenging. Until the vaccination rate of veterinary rabies vaccines in China reaches a high level, post-exposure prophylaxis measures remain necessary after animal bites, indicating that the rabies vaccine market in China still holds significant growth potential.
mRNA vaccine production is rapid and cost-effective, with flexibility in antigen design, making it an important pathway for preventive vaccine development. Internationally, mRNA rabies vaccines under development have shown good protective effects and tolerability in existing studies.
