PMID- 37210308
OWN - NLM
STAT- MEDLINE
DCOM- 20230614
LR  - 20231213
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 41
IP  - 26
DP  - 2023 Jun 13
TI  - 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.
PG  - 3898-3906
LID - S0264-410X(23)00488-7 [pii]
LID - 10.1016/j.vaccine.2023.04.064 [doi]
AB  - 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 mug, 50 mug, and 
      100 mug) 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 mug, 53.8 (26.8-108.1) for mRNA-1388 50 mug, 92.8 
      (43.6-197.6) for mRNA-1388 100 mug, 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.
CI  - Copyright (c) 2023. Published by Elsevier Ltd.
FAU - Shaw, Christine A
AU  - Shaw CA
AD  - Moderna, Inc., Cambridge, MA, USA.
FAU - August, Allison
AU  - August A
AD  - Moderna, Inc., Cambridge, MA, USA.
FAU - Bart, Stephan
AU  - Bart S
AD  - Trial Professionals Consultant Group Inc., USA.
FAU - Booth, Peta-Gay Jackson
AU  - Booth PJ
AD  - Optimal Research, Rockville, MD, USA.
FAU - Knightly, Conor
AU  - Knightly C
AD  - Moderna, Inc., Cambridge, MA, USA.
FAU - Brasel, Trevor
AU  - Brasel T
AD  - University of Texas Medical Branch, Galveston, TX, USA.
FAU - Weaver, Scott C
AU  - Weaver SC
AD  - University of Texas Medical Branch, Galveston, TX, USA.
FAU - Zhou, HongHong
AU  - Zhou H
AD  - Moderna, Inc., Cambridge, MA, USA.
FAU - Panther, Lori
AU  - Panther L
AD  - Moderna, Inc., Cambridge, MA, USA. Electronic address: 
      Lori.Panther@modernatx.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03325075
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230518
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Antibodies, Viral)
SB  - IM
MH  - Humans
MH  - Adult
MH  - *Chikungunya virus
MH  - *Chikungunya Fever/prevention & control
MH  - Vaccines, Synthetic
MH  - Antibodies, Neutralizing
MH  - Antibodies, Viral
MH  - Immunogenicity, Vaccine
MH  - Double-Blind Method
MH  - mRNA Vaccines
OTO - NOTNLM
OT  - Binding antibodies
OT  - Chikungunya virus
OT  - Neutralizing antibodies
OT  - Safety
OT  - Vaccine
OT  - mRNA
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: A.A., C.A.S., C.K., H.Z., and L.P. are employees of Moderna, Inc., and 
      may hold stock/stock options in the company. S.B., P.-G.J.B., T.B., and S.W. have 
      no relevant or material financial interests that relate to the research described 
      in this article.
EDAT- 2023/05/21 01:05
MHDA- 2023/06/14 06:42
CRDT- 2023/05/20 22:01
PHST- 2021/12/21 00:00 [received]
PHST- 2023/03/27 00:00 [revised]
PHST- 2023/04/24 00:00 [accepted]
PHST- 2023/06/14 06:42 [medline]
PHST- 2023/05/21 01:05 [pubmed]
PHST- 2023/05/20 22:01 [entrez]
AID - S0264-410X(23)00488-7 [pii]
AID - 10.1016/j.vaccine.2023.04.064 [doi]
PST - ppublish
SO  - Vaccine. 2023 Jun 13;41(26):3898-3906. doi: 10.1016/j.vaccine.2023.04.064. Epub 
      2023 May 18.