BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×1010 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS:Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose ofplacebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).
RCT Entities:
BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×1010 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], -49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, -76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).
Authors: Hannah Wang; Jacob A Miller; Michelle Verghese; Mamdouh Sibai; Daniel Solis; Kenji O Mfuh; Becky Jiang; Naomi Iwai; Marilyn Mar; ChunHong Huang; Fumiko Yamamoto; Malaya K Sahoo; James Zehnder; Benjamin A Pinsky Journal: J Clin Microbiol Date: 2021-07-19 Impact factor: 5.948
Authors: David R Martinez; Alexandra Schäfer; Sophie Gobeil; Dapeng Li; Gabriela De la Cruz; Robert Parks; Xiaozhi Lu; Maggie Barr; Victoria Stalls; Katarzyna Janowska; Esther Beaudoin; Kartik Manne; Katayoun Mansouri; Robert J Edwards; Kenneth Cronin; Boyd Yount; Kara Anasti; Stephanie A Montgomery; Juanjie Tang; Hana Golding; Shaunna Shen; Tongqing Zhou; Peter D Kwong; Barney S Graham; John R Mascola; David C Montefiori; S Munir Alam; Gregory Sempowski; Gregory D Sempowski; Surender Khurana; Kevin Wiehe; Kevin O Saunders; Priyamvada Acharya; Barton F Haynes; Ralph S Baric Journal: Sci Transl Med Date: 2022-01-26 Impact factor: 17.956
Authors: Milankumar Patel; Farah Shahjin; Jacob D Cohen; Mahmudul Hasan; Jatin Machhi; Heerak Chugh; Snigdha Singh; Srijanee Das; Tanmay A Kulkarni; Jonathan Herskovitz; Douglas D Meigs; Ramesh Chandra; Kenneth S Hettie; R Lee Mosley; Bhavesh D Kevadiya; Howard E Gendelman Journal: FEMS Microbiol Rev Date: 2021-11-23 Impact factor: 16.408
Authors: Richard Copin; Alina Baum; Elzbieta Wloga; Kristen E Pascal; Stephanie Giordano; Benjamin O Fulton; Anbo Zhou; Nicole Negron; Kathryn Lanza; Newton Chan; Angel Coppola; Joyce Chiu; Min Ni; Yi Wei; Gurinder S Atwal; Annabel Romero Hernandez; Kei Saotome; Yi Zhou; Matthew C Franklin; Andrea T Hooper; Shane McCarthy; Sara Hamon; Jennifer D Hamilton; Hilary M Staples; Kendra Alfson; Ricardo Carrion; Shazia Ali; Thomas Norton; Selin Somersan-Karakaya; Sumathi Sivapalasingam; Gary A Herman; David M Weinreich; Leah Lipsich; Neil Stahl; Andrew J Murphy; George D Yancopoulos; Christos A Kyratsous Journal: Cell Date: 2021-06-05 Impact factor: 41.582