tetano
Editor, Senior Moderator
Nat Commun
. 2024 May 14;15(1):4081.
doi: 10.1038/s41467-024-47905-1. Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
Nhân Thị Hồ[SUP] 1 [/SUP], Steven G Hughes[SUP] 2 [/SUP], Van Thanh Ta[SUP] 3 [/SUP], Lân Trọng Phan[SUP] 4 [/SUP], Quyết Đỗ[SUP] 5 [/SUP], Thượng Vũ Nguyễn[SUP] 4 [/SUP], Anh Thị Văn Phạm[SUP] 3 [/SUP], Mai Thị Ngọc Đặng[SUP] 3 [/SUP], Lượng Viết Nguyễn[SUP] 5 [/SUP], Quang Vinh Trịnh[SUP] 3 [/SUP], Hùng Ngọc Phạm[SUP] 5 [/SUP], Mến Văn Chử[SUP] 5 [/SUP], Toàn Trọng Nguyễn[SUP] 4 [/SUP], Quang Chấn Lương[SUP] 4 [/SUP], Vy Thị Tường Lê[SUP] 4 [/SUP], Thắng Văn Nguyễn[SUP] 5 [/SUP], Lý-Thi-Lê Trần[SUP] 6 7 [/SUP], Anh Thi Van Luu[SUP] 7 [/SUP], Anh Ngoc Nguyen[SUP] 7 [/SUP], Nhung-Thi-Hong Nguyen[SUP] 1 [/SUP], Hai-Son Vu[SUP] 1 [/SUP], Jonathan M Edelman[SUP] 8 [/SUP], Suezanne Parker[SUP] 2 [/SUP], Brian Sullivan[SUP] 2 [/SUP], Sean Sullivan[SUP] 2 [/SUP], Qian Ruan[SUP] 2 [/SUP], Brenda Clemente[SUP] 2 [/SUP], Brian Luk[SUP] 2 [/SUP], Kelly Lindert[SUP] 2 [/SUP], Dina Berdieva[SUP] 2 [/SUP], Kat Murphy[SUP] 2 [/SUP], Rose Sekulovich[SUP] 2 [/SUP], Benjamin Greener[SUP] 2 [/SUP], Igor Smolenov[SUP] 2 [/SUP], Pad Chivukula[SUP] 2 [/SUP], Vân Thu Nguyễn[SUP] 7 [/SUP], Xuan-Hung Nguyen[SUP] 9 10 11 [/SUP]
Affiliations
Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.
. 2024 May 14;15(1):4081.
doi: 10.1038/s41467-024-47905-1. Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
Nhân Thị Hồ[SUP] 1 [/SUP], Steven G Hughes[SUP] 2 [/SUP], Van Thanh Ta[SUP] 3 [/SUP], Lân Trọng Phan[SUP] 4 [/SUP], Quyết Đỗ[SUP] 5 [/SUP], Thượng Vũ Nguyễn[SUP] 4 [/SUP], Anh Thị Văn Phạm[SUP] 3 [/SUP], Mai Thị Ngọc Đặng[SUP] 3 [/SUP], Lượng Viết Nguyễn[SUP] 5 [/SUP], Quang Vinh Trịnh[SUP] 3 [/SUP], Hùng Ngọc Phạm[SUP] 5 [/SUP], Mến Văn Chử[SUP] 5 [/SUP], Toàn Trọng Nguyễn[SUP] 4 [/SUP], Quang Chấn Lương[SUP] 4 [/SUP], Vy Thị Tường Lê[SUP] 4 [/SUP], Thắng Văn Nguyễn[SUP] 5 [/SUP], Lý-Thi-Lê Trần[SUP] 6 7 [/SUP], Anh Thi Van Luu[SUP] 7 [/SUP], Anh Ngoc Nguyen[SUP] 7 [/SUP], Nhung-Thi-Hong Nguyen[SUP] 1 [/SUP], Hai-Son Vu[SUP] 1 [/SUP], Jonathan M Edelman[SUP] 8 [/SUP], Suezanne Parker[SUP] 2 [/SUP], Brian Sullivan[SUP] 2 [/SUP], Sean Sullivan[SUP] 2 [/SUP], Qian Ruan[SUP] 2 [/SUP], Brenda Clemente[SUP] 2 [/SUP], Brian Luk[SUP] 2 [/SUP], Kelly Lindert[SUP] 2 [/SUP], Dina Berdieva[SUP] 2 [/SUP], Kat Murphy[SUP] 2 [/SUP], Rose Sekulovich[SUP] 2 [/SUP], Benjamin Greener[SUP] 2 [/SUP], Igor Smolenov[SUP] 2 [/SUP], Pad Chivukula[SUP] 2 [/SUP], Vân Thu Nguyễn[SUP] 7 [/SUP], Xuan-Hung Nguyen[SUP] 9 10 11 [/SUP]
Affiliations
- PMID: 38744844
- DOI: 10.1038/s41467-024-47905-1
Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.