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. Shaw, C. A., August, A., Bart, S., Booth, P. G. J., Knightly, C., Brasel, T., Weaver, S. C., Zhou, H. H., & Panther, L. Vaccine, 41(26):3898–3906, 2023. Publisher: Elsevier Ltd![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 [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{shaw_phase_2023,
title = {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},
volume = {41},
issn = {18732518},
url = {https://doi.org/10.1016/j.vaccine.2023.04.064},
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.},
number = {26},
journal = {Vaccine},
author = {Shaw, Christine A. and August, Allison and Bart, Stephan and Booth, Peta Gay Jackson and Knightly, Conor and Brasel, Trevor and Weaver, Scott C. and Zhou, Hong Hong and Panther, Lori},
year = {2023},
pmid = {37210308},
note = {Publisher: Elsevier Ltd},
keywords = {Binding antibodies, Chikungunya virus, Neutralizing antibodies, Safety, Vaccine, mRNA},
pages = {3898--3906},
}
Downloads: 0
{"_id":"A8Lv8hm5JY3XeGiBq","bibbaseid":"shaw-august-bart-booth-knightly-brasel-weaver-zhou-etal-aphase1randomizedplacebocontrolleddoserangingstudytoevaluatethesafetyandimmunogenicityofanmrnabasedchikungunyavirusvaccineinhealthyadults-2023","author_short":["Shaw, C. A.","August, A.","Bart, S.","Booth, P. G. J.","Knightly, C.","Brasel, T.","Weaver, S. C.","Zhou, H. H.","Panther, L."],"bibdata":{"bibtype":"article","type":"article","title":"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","volume":"41","issn":"18732518","url":"https://doi.org/10.1016/j.vaccine.2023.04.064","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.","number":"26","journal":"Vaccine","author":[{"propositions":[],"lastnames":["Shaw"],"firstnames":["Christine","A."],"suffixes":[]},{"propositions":[],"lastnames":["August"],"firstnames":["Allison"],"suffixes":[]},{"propositions":[],"lastnames":["Bart"],"firstnames":["Stephan"],"suffixes":[]},{"propositions":[],"lastnames":["Booth"],"firstnames":["Peta","Gay","Jackson"],"suffixes":[]},{"propositions":[],"lastnames":["Knightly"],"firstnames":["Conor"],"suffixes":[]},{"propositions":[],"lastnames":["Brasel"],"firstnames":["Trevor"],"suffixes":[]},{"propositions":[],"lastnames":["Weaver"],"firstnames":["Scott","C."],"suffixes":[]},{"propositions":[],"lastnames":["Zhou"],"firstnames":["Hong","Hong"],"suffixes":[]},{"propositions":[],"lastnames":["Panther"],"firstnames":["Lori"],"suffixes":[]}],"year":"2023","pmid":"37210308","note":"Publisher: Elsevier Ltd","keywords":"Binding antibodies, Chikungunya virus, Neutralizing antibodies, Safety, Vaccine, mRNA","pages":"3898–3906","bibtex":"@article{shaw_phase_2023,\n\ttitle = {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},\n\tvolume = {41},\n\tissn = {18732518},\n\turl = {https://doi.org/10.1016/j.vaccine.2023.04.064},\n\tdoi = {10.1016/j.vaccine.2023.04.064},\n\tabstract = {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.},\n\tnumber = {26},\n\tjournal = {Vaccine},\n\tauthor = {Shaw, Christine A. and August, Allison and Bart, Stephan and Booth, Peta Gay Jackson and Knightly, Conor and Brasel, Trevor and Weaver, Scott C. and Zhou, Hong Hong and Panther, Lori},\n\tyear = {2023},\n\tpmid = {37210308},\n\tnote = {Publisher: Elsevier Ltd},\n\tkeywords = {Binding antibodies, Chikungunya virus, Neutralizing antibodies, Safety, Vaccine, mRNA},\n\tpages = {3898--3906},\n}\n\n\n\n","author_short":["Shaw, C. A.","August, A.","Bart, S.","Booth, P. G. J.","Knightly, C.","Brasel, T.","Weaver, S. C.","Zhou, H. H.","Panther, L."],"key":"shaw_phase_2023-1","id":"shaw_phase_2023-1","bibbaseid":"shaw-august-bart-booth-knightly-brasel-weaver-zhou-etal-aphase1randomizedplacebocontrolleddoserangingstudytoevaluatethesafetyandimmunogenicityofanmrnabasedchikungunyavirusvaccineinhealthyadults-2023","role":"author","urls":{"Paper":"https://doi.org/10.1016/j.vaccine.2023.04.064"},"keyword":["Binding antibodies","Chikungunya virus","Neutralizing antibodies","Safety","Vaccine","mRNA"],"metadata":{"authorlinks":{}},"html":""},"bibtype":"article","biburl":"https://bibbase.org/zotero/FRGBergamini","dataSources":["o2mL7kG99iAQPpNRJ"],"keywords":["binding antibodies","chikungunya virus","neutralizing antibodies","safety","vaccine","mrna"],"search_terms":["phase","randomized","placebo","controlled","dose","ranging","study","evaluate","safety","immunogenicity","mrna","based","chikungunya","virus","vaccine","healthy","adults","shaw","august","bart","booth","knightly","brasel","weaver","zhou","panther"],"title":"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","year":2023}