A phase 1, randomized, placebo-controlled, dose-ranging study to evaluate the safety and immunogenicity of an mRNA-based chikungunya virus vaccine in healthy adults.

Abstract

BACKGROUND:

Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikungunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region.

METHODS:

This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18-49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 μg, 50 μg, and 100 μg) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated.

RESULTS:

Sixty participants were randomized and received ≥ 1 vaccination; 54 (90 %) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95 % confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1-7.6) for mRNA-1388 25 μg, 53.8 (26.8-108.1) for mRNA-1388 50 μg, 92.8 (43.6-197.6) for mRNA-1388 100 μg, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutralizing antibodies.

CONCLUSIONS:

mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substantial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region.

CLINICALTRIALS:

gov: NCT03325075.

• Authors: Christine A Shaw, Allison August, Stephan Bart, Peta-Gay Jackson Booth, Conor Knightly, Trevor Brasel, Scott C Weaver, HongHong Zhou, Lori Panther
• Journal: Vaccine (Vaccine) Vol. 41 Issue 26 Pg. 3898-3906 (06 13 2023) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 37210308 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Ltd.

Chemical References

• mRNA Vaccine
• Vaccines, Synthetic
• Antibodies, Neutralizing
• Antibodies, Viral

Topics

• Humans
• Adult
• Chikungunya virus
• Chikungunya Fever (prevention & control)
• Vaccines, Synthetic
• Antibodies, Neutralizing
• Antibodies, Viral
• Immunogenicity, Vaccine
• Double-Blind Method