mRNA rabies vaccine induces durable immune responses in macaque monkeys

In a recent study published in Nature CommunicationsResearchers are investigating the effects of a rabies messenger ribonucleic acid (mRNA) vaccine on B cell memory responses and cross-neutralizing antibody titers.

study: An unmodified rabies mRNA vaccine induces high cross-neutralizing antibody titers and diverse B-cell memory responses. Image credit: Kateryna Kon / Shutterstock.com

new rabies vaccine

Rabies virus (RABV) is primarily transmitted to humans through bites from infected animals. Recently, a vaccine consisting of a specific sequence of nucleoside-unmodified mRNA encoding RABV-G complexed within protamine has Neutralizing antibody It effectively protects vaccinated individuals from lethal RABV infection in various animal models.

In this study, we investigated the quality and characteristics of the immune response induced by this RABV-G mRNA vaccine compared to the whole inactivated virus vaccine, Rabipur. Immunizing non-human primates (NHPs) with high-dose mRNA vaccines, he analyzed responses from early innate immune activation to the quality and titer of antibodies collected up to 1 year later.

About research

A total of 18 rhesus monkeys were included in the study and divided into three groups based on weight and sex. Groups 1 and 2 received 100 μg mRNA vaccine, and group 3 received Rabipur. Groups 2 and 3 received his second dose of each vaccine 4 weeks after his first dose and compared the responses of his two groups that underwent similar immunization processes.

The vaccine was administered by intramuscular injection. Peripheral blood samples and bone marrow aspirates were collected at various intervals throughout the 50-week study.

research result

mRNA vaccination increased levels of circulating interferon-α (IFNα) and IFN-induced I-TAC/CXCL11, neither of which was detected in Rabipur recipients. In addition, the mRNA vaccine produced higher levels of interleukin-1 receptor antagonist (IL-1RA), chemokine eotaxin, and monocyte chemoattractant protein 1 (MCP-1) compared to baseline values.

Immunization with either vaccine did not cause significant changes in complete blood counts (CBC) or clinical chemistry, nor did the vaccines increase body temperature or adversely affect body weight.

Almost all animals developed rabies virus neutralizing antibody (RVNA) titers above the threshold recommended by the World Health Organization (WHO) two weeks after the first immunization. Unlike the mRNA-vaccinated cohort, the rabipur group showed a decline in titers 4 weeks after the first vaccination.

At week 18, all three cohorts had RVNA titers above the WHO threshold. Only boost mRNA vaccinees showed consistently high antibody titers throughout the 50-week study period. The kinetics of RABV-G-binding immunoglobulin G (IgG) titers were similar to neutralizing titers. After vaccination, all cohorts showed detectable levels of her RABV-G-specific IgM.

Plasmablasts secreting antibodies specific for RABV-G were detected by ELISpot 4 days after the boost. To this end, the mRNA prime-boost cohort had a higher frequency of these plasmablasts compared to the Rabipur cohort.

After the first immunization, all groups showed detectable RABV-G-specific plasma cells in the bone marrow. Notably, RABV-G-specific circulating memory B cells (MBC) increased after boosting in the mRNA group and remained detectable for 18 weeks thereafter. Moreover, MBC-derived antibody-secreting cells were still detectable in the mRNA groups, especially in the prime-boost cohort, even at 50 weeks.

mRNA vaccine recipients showed a reduction in CD4+ T cells Reactions after first vaccination. However, although these T cell levels increased after booster vaccination, no CD4+ T cell responses were detected in Rabipur recipients. All groups showed undetectable or low CD8+ T cell responses.

From 2 weeks post-boost to 12 weeks post-boost, there was a gradual increase in mean somatic hypermutation (SHM) per animal for RABV-G-specific MBC observed in both groups. No significant variation in SHM was detected between groups.

Conclusion

A two-dose strategy using mRNA vaccines resulted in higher antibody titers and higher RABV-G-specific cell populations compared to inactivated virus vaccines. Similarly, mRNA vaccination elicited a stronger immune response than Rabipur vaccine when given twice on the same 4-week interval schedule. The mRNA vaccine also induced higher frequencies of B cells and plasma cells, as well as stronger neutralization.

These findings indicate that this type of mRNA vaccine may be a valuable alternative to currently licensed rabies vaccines for pre-exposure and post-exposure prophylaxis.