tetano
Editor, Senior Moderator
NPJ Vaccines
. 2022 Dec 13;7(1):161.
doi: 10.1038/s41541-022-00590-x.
A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine
Jenny G Low[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ruklanthi de Alwis[SUP] #[/SUP][SUP] 1 3 [/SUP], Shiwei Chen[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 1 2 [/SUP], Yan Shan Leong[SUP] 1 3 [/SUP], Tania Ken Lin Mah[SUP] 1 3 [/SUP], Natalene Yuen[SUP] 3 4 [/SUP], Hwee Cheng Tan[SUP] 1 [/SUP], Summer L Zhang[SUP] 1 [/SUP], Jean X Y Sim[SUP] 2 [/SUP], Yvonne F Z Chan[SUP] 2 [/SUP], Ayesa Syenina[SUP] 1 3 [/SUP], Jia Xin Yee[SUP] 1 3 [/SUP], Eugenia Z Ong[SUP] 1 3 [/SUP], Rose Sekulovich[SUP] 5 [/SUP], Brian B Sullivan[SUP] 5 [/SUP], Kelly Lindert[SUP] 5 [/SUP], Sean M Sullivan[SUP] 5 [/SUP], Pad Chivukula[SUP] 5 [/SUP], Steven G Hughes[SUP] 6 [/SUP], Eng Eong Ooi[SUP] 1 3 [/SUP]
Affiliations
Abstract
Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial (N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N = 64) tested two-doses of ARCT-021 given 28 days apart. During phase 1, ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness were more common in ARCT-021vaccinated, while systemic solicited AEs, mainly fatigue, headache and myalgia were reported in 62.8% and 46.4% of ARCT-021 and placebo recipients, respectively. Seroconversion rate for anti-S IgG was 100% in all cohorts, except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults. Anti-S IgG and neutralizing antibody titers showed a general increase with increasing dose, and overlapped with titers in Covid-19 convalescent patients. T-cell responses were also observed in response to stimulation with S-protein peptides. Taken collectively, ARCT-021 is immunogenic and has favorable safety profile for further development.
. 2022 Dec 13;7(1):161.
doi: 10.1038/s41541-022-00590-x.
A phase I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine
Jenny G Low[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Ruklanthi de Alwis[SUP] #[/SUP][SUP] 1 3 [/SUP], Shiwei Chen[SUP] 1 [/SUP], Shirin Kalimuddin[SUP] 1 2 [/SUP], Yan Shan Leong[SUP] 1 3 [/SUP], Tania Ken Lin Mah[SUP] 1 3 [/SUP], Natalene Yuen[SUP] 3 4 [/SUP], Hwee Cheng Tan[SUP] 1 [/SUP], Summer L Zhang[SUP] 1 [/SUP], Jean X Y Sim[SUP] 2 [/SUP], Yvonne F Z Chan[SUP] 2 [/SUP], Ayesa Syenina[SUP] 1 3 [/SUP], Jia Xin Yee[SUP] 1 3 [/SUP], Eugenia Z Ong[SUP] 1 3 [/SUP], Rose Sekulovich[SUP] 5 [/SUP], Brian B Sullivan[SUP] 5 [/SUP], Kelly Lindert[SUP] 5 [/SUP], Sean M Sullivan[SUP] 5 [/SUP], Pad Chivukula[SUP] 5 [/SUP], Steven G Hughes[SUP] 6 [/SUP], Eng Eong Ooi[SUP] 1 3 [/SUP]
Affiliations
- PMID: 36513697
- DOI: 10.1038/s41541-022-00590-x
Abstract
Coronavirus disease-19 (Covid-19) pandemic have demonstrated the importantance of vaccines in disease prevention. Self-amplifying mRNA vaccines could be another option for disease prevention if demonstrated to be safe and immunogenic. Phase 1 of this randomized, double-blinded, placebo-controlled trial (N = 42) assessed the safety, tolerability, and immunogenicity in healthy young and older adults of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N = 64) tested two-doses of ARCT-021 given 28 days apart. During phase 1, ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness were more common in ARCT-021vaccinated, while systemic solicited AEs, mainly fatigue, headache and myalgia were reported in 62.8% and 46.4% of ARCT-021 and placebo recipients, respectively. Seroconversion rate for anti-S IgG was 100% in all cohorts, except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults. Anti-S IgG and neutralizing antibody titers showed a general increase with increasing dose, and overlapped with titers in Covid-19 convalescent patients. T-cell responses were also observed in response to stimulation with S-protein peptides. Taken collectively, ARCT-021 is immunogenic and has favorable safety profile for further development.