mRNA vaccines for the prevention of infectious diseases: A review of international experience in evaluating efficacy and safety based on clinical trial results

INTRODUCTION. The mRNA platform technology for creating vaccines against infectious diseases was introduced into clinical practice during the COVID-19 pandemic; however, the accumulated experience of clinical use of mRNA vaccines requires systematization in relation to other infectious diseases. Therefore, summarizing data on the efficacy and safety of such mRNA vaccines in controlled clinical trials is relevant for substantiating approaches to the regulatory evaluation of immunobiological medicinal products of this class.

AIM. To review the results of clinical trials of mRNA vaccines for the prevention of respiratory syncytial virus infection (RSV infection), cytomegalovirus infection (CMV infection), seasonal influenza, Zika fever, and rabies to summarize data on their efficacy and safety, identifying the limitations associated with the use of surrogate endpoints and sample size.

DISCUSSION. The authors analyzed publications in PubMed, eLIBRARY.RU and records in ClinicalTrials.gov describing the results of controlled clinical trials of mRNA vaccines for the prevention of infectious diseases (excluding COVID-19) from 2016 to 2026. Clinical efficacy was confirmed only for the mRNA-1345 vaccine against RSV infection: 83.7% (for episodes with 2 symptoms) and 82.4% (for episodes with 3 symptoms); the safety profile was considered satisfactory. For mRNA vaccines against seasonal influenza, a favorable safety profile and pronounced seroconversion in the hemagglutination inhibition assay were confirmed; the humoral immunity parameters were comparable to those of licensed vaccines. The mRNA-1647 vaccine against CMV infection, after a three-dose regimen, induced a durable immune response with the activation of T-cell immunity, along with a favorable safety profile. In a study of vaccines for the prevention of Zika fever (mRNA-1325, mRNA-1893), the presence of neutralizing antibodies (in a neutralization assay) after vaccination was demonstrated in participants with different baseline flavivirus serostatus; the safety profile was considered favorable. The mRNA vaccine CV7201 against rabies induced protective titers of virus-neutralizing antibodies in 71% of study participants after intradermal administration and in 46% after intramuscular administration; the incidence of local and systemic adverse events (AEs) was high (97% and 78%, respectively). Most studies were shown to have limitations associated with the assessment of efficacy using surrogate endpoints and an insufficient sample size to detect rare adverse events.

CONCLUSIONS. The results of controlled clinical trials of mRNA vaccines for the prevention of RSV and CMV infection, seasonal influenza, Zika fever, and rabies demonstrated their potential efficacy and acceptable safety profile; however, the evaluation of most products is based on surrogate endpoints and small sample sizes, which are the main limitations of the conducted studies. The findings substantiate the need for further research using endpoints (clinical efficacy, surrogate markers) and post-marketing safety monitoring (primarily for local and systemic AEs).

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