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

Christine A Shaw; Allison August; Stephan Bart; Peta-Gay Jackson Booth; Conor Knightly; Trevor Brasel; Scott C Weaver; HongHong Zhou; Lori Panther

doi:10.1016/j.vaccine.2023.04.064

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

Vaccine. 2023 Jun 13;41(26):3898-3906. doi: 10.1016/j.vaccine.2023.04.064. Epub 2023 May 18.

Authors

Christine A Shaw¹, Allison August¹, Stephan Bart², Peta-Gay Jackson Booth³, Conor Knightly¹, Trevor Brasel⁴, Scott C Weaver⁴, HongHong Zhou¹, Lori Panther⁵

Affiliations

¹ Moderna, Inc., Cambridge, MA, USA.
² Trial Professionals Consultant Group Inc., USA.
³ Optimal Research, Rockville, MD, USA.
⁴ University of Texas Medical Branch, Galveston, TX, USA.
⁵ Moderna, Inc., Cambridge, MA, USA. Electronic address: Lori.Panther@modernatx.com.

PMID: 37210308
DOI: 10.1016/j.vaccine.2023.04.064

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.

Keywords: Binding antibodies; Chikungunya virus; Neutralizing antibodies; Safety; Vaccine; mRNA.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Neutralizing
Antibodies, Viral
Chikungunya Fever* / prevention & control
Chikungunya virus*
Double-Blind Method
Humans
Immunogenicity, Vaccine
Vaccines, Synthetic
mRNA Vaccines

Substances

Vaccines, Synthetic
Antibodies, Neutralizing
Antibodies, Viral

Associated data

ClinicalTrials.gov/NCT03325075