Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant

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Abstract

Background

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use.

Methods

In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 μg recombinant spike protein with 50 μg Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy ≥7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants.

Results

A total of 4387 participants were randomized and dosed at least once, 2199 with NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH), 15 and 29 predominantly mild to moderate Covid-19 cases were noted in NVX-CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to 80.1) and did not differ by baseline serostatus; 38 (92.7%) of 41 sequenced cases were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: −0.6 to 76.2) in HIV-negative participants. Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373; serious adverse events were rare in both groups.

Conclusions

The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant.

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Most cited references 20

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Merryn Voysey, Sue Ann Costa Clemens, Shabir Madhi … (2022)

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

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Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding

Tyler N. Starr, Allison J. Greaney, Sarah K Hilton … (2021)

Summary The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor, and is a major determinant of host range and a dominant target of neutralizing antibodies. Here we experimentally measure how all amino-acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.

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Author and article information

Journal

Journal ID (nlm-ta): N Engl J Med

Journal ID (iso-abbrev): N Engl J Med

Title: The New England Journal of Medicine

Publisher: Massachusetts Medical Society

ISSN (Print): 0028-4793

ISSN (Electronic): 1533-4406

Publication date (Print): 20 May 2021

Publication date (Electronic): 06 May 2021

Publication date PMC-release: 06 May 2021

Volume: 384

Issue: 20

Pages: 1899-1909

Affiliations

[1 ]Novavax, Inc., 20 Firstfield Road, Gaithersburg, MD, USA

[2 ]South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

[3 ]Josha Research Centre, Bloemfontein, Free State, South Africa

[4 ]Paediatric Infectious Diseases Unit, University of KwaZulu-Natal, Durban, South Africa

[5 ]Soweto Clinical Trials Centre, Johannesburg, South Africa

[6 ]Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa

[7 ]Respiratory and Critical Care Unit, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

[8 ]Setshaba Research Centre, Tshwane, South Africa

[9 ]Department of Obstetrics and Gynaecology, University of KwaZulu-Natal, Durban, South Africa

[10 ]Centre Aids Prevention Research South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa

[11 ]Limpopo Clinical Research Initiative, Rustenburg, North-West, South Africa

[12 ]Madibeng Centre for Research, Department of Family Medicine, School of Health, University of Pretoria, Pretoria, South Africa

[13 ]South African TB Vaccine Initiative, University of Cape Town, Cape Town, South Africa

[14 ]Health Systems Research Unit and HIV Prevention Research Unit, South African Medical Research Council, Cape Town, South Africa

[15 ]Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute, University of Cape Town, Cape Town, South Africa

[16 ]Aurum Institute, University of Pretoria, Pretoria, South Africa

[17 ]MERC Research, Middelburg, South Africa

[18 ]PEERMED Clinical Trial Centre, Kempton Park, South Africa

[19 ]Kwazulu-Natal Research Innovation and Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, South Africa

Author notes

Contact information for corresponding author: Vivek Shinde at Novavax, 21 Firstfield Rd., Gaithersburg, MD, 20878, or vshinde@ 123456novavax.com .

This is an Author Final Manuscript, which is the version after external peer review and before publication in the Journal. The publisher’s version of record, which includes all New England Journal of Medicine editing and enhancements, is available at 10.1056/NEJMoa2103055.

Article

DOI: 10.1056/NEJMoa2103055

PMC ID: 8091623

PubMed ID: 33951374

SO-VID: cb4b113f-9366-454d-a706-b4bc43e91ec0

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This Author Accepted Manuscript is licensed for use under the CC-BY license.

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Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant

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Abstract

Background

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Most cited references 20

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding

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