Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(25), P. 2439 - 2450

Published: Oct. 14, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no is currently available. Interim safety immunogenicity data about candidate BNT162b1 in younger adults been reported previously from trials Germany United States.In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted States, we randomly assigned healthy 18 55 years age those 65 85 receive either placebo or one two lipid nanoparticle-formulated, nucleoside-modified RNA candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain; BNT162b2, membrane-anchored full-length spike, stabilized prefusion conformation. The primary outcome was (e.g., local systemic reactions adverse events); secondary outcome. Trial groups were defined according candidate, participants, dose level (10 μg, 20 30 100 μg). In all one, participants received doses, with 21-day interval between doses; group (100 μg BNT162b1), dose.A total 195 underwent randomization. each 13 15 12 3 placebo. BNT162b2 associated lower incidence severity than particularly older adults. both adults, elicited similar dose-dependent SARS-CoV-2-neutralizing geometric mean titers, higher titer panel convalescent serum samples.The this U.S. added earlier interim regarding support selection for advancement pivotal 2-3 efficacy evaluation. (Funded by BioNTech Pfizer; ClinicalTrials.gov number, NCT04368728.).

Language: Английский

---

SARS-CoV-2 vaccines in development

Nature, Journal Year: 2020, Volume and Issue: 586(7830), P. 516 - 527

Published: Sept. 23, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 China and is the causative agent of disease (COVID-19) pandemic. To mitigate effects virus on public health, economy society, a vaccine urgently needed. Here I review development vaccines against SARS-CoV-2. Development initiated when genetic sequence became available early January 2020, has moved at an unprecedented speed: phase trial started March 2020 there are currently more than 180 various stages development. Data from II trials already for several candidates, many have into III trials. The data so far suggest that effective safe might become within months, rather years.

Language: Английский

---

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Nature, Journal Year: 2020, Volume and Issue: 586(7830), P. 594 - 599

Published: Sept. 30, 2020

Language: Английский

---

Spike mutation D614G alters SARS-CoV-2 fitness

Nature, Journal Year: 2020, Volume and Issue: 592(7852), P. 116 - 121

Published: Oct. 26, 2020

Language: Английский

---

Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data

The Lancet, Journal Year: 2021, Volume and Issue: 397(10287), P. 1819 - 1829

Published: May 1, 2021

Language: Английский

---

Measuring the impact of COVID-19 vaccine misinformation on vaccination intent in the UK and USA

Nature Human Behaviour, Journal Year: 2021, Volume and Issue: 5(3), P. 337 - 348

Published: Feb. 5, 2021

Language: Английский

---

Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 383(24), P. 2320 - 2332

Published: Sept. 2, 2020

NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.We initiated randomized, placebo-controlled, phase 1-2 trial to evaluate the safety immunogenicity rSARS-CoV-2 (in 5-μg 25-μg doses, with or without adjuvant, observers unaware trial-group assignments) in 131 healthy adults. In 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry hematology), according Food Drug Administration toxicity scoring, assess safety; IgG anti-spike protein response enzyme-linked immunosorbent assay [ELISA] units). Secondary included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), T-cell responses (cytokine staining). microneutralization results compared 32 (IgG) 29 (neutralization) convalescent serum samples from patients Covid-19, most whom symptomatic. We performed analysis at day 35.After randomization, 83 participants assigned receive adjuvant 25 23 placebo. No serious events noted. Reactogenicity was absent mild majority participants, more common short duration (mean, ≤2 days). One participant had fever that lasted 1 day. Unsolicited participants; there no events. addition resulted enhanced immune responses, antigen dose-sparing, induced T helper (Th1) response. two-dose adjuvanted regimen geometric mean (63,160 ELISA units) (3906) exceeded mostly symptomatic Covid-19 (8344 983, respectively).At 35 days, appeared be safe, it elicited levels serum. CD4+ biased toward Th1 phenotype. (Funded by Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

Language: Английский

---

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(11), P. 2032 - 2040

Published: Sept. 29, 2021

Abstract The global supply of COVID-19 vaccines remains limited. An understanding the immune response that is predictive protection could facilitate rapid licensure new vaccines. Data from a randomized efficacy trial ChAdOx1 nCoV-19 (AZD1222) vaccine in United Kingdom was analyzed to determine antibody levels associated with against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after second dose were measured infected noninfected recipients. Higher all markers correlated reduced risk symptomatic infection. A 80% infection majority Alpha (B.1.1.7) variant SARS-CoV-2 achieved 264 (95% CI: 108, 806) binding units (BAU)/ml: 506 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike anti-RBD antibodies, 26 NC, NC) international unit (IU)/ml 247 101, normalized neutralization titers (NF 50 ) pseudovirus live-virus neutralization, respectively. Immune asymptomatic infections 5% significance level. These can be used bridge populations using validated assays, allow extrapolation estimates

Language: Английский

---

Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(19), P. 1824 - 1835

Published: Jan. 13, 2021

Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding full-length and stabilized SARS-CoV-2 spike protein.In this multicenter, placebo-controlled, phase 1-2a trial, we randomly assigned healthy adults between ages 18 55 years (cohort 1) those 65 age or older 3) receive Ad26.COV2.S vaccine at dose 5×1010 viral particles (low dose) 1×1011 (high per milliliter placebo in single-dose two-dose schedule. Longer-term data comparing regimen being collected cohort 2; results not reported here. The primary end points were safety reactogenicity each schedule.After administration first 805 participants cohorts 1 3 after second 1, most frequent solicited adverse events fatigue, headache, myalgia, injection-site pain. systemic event was fever. Systemic less common than who received low high dose. Reactogenicity lower Neutralizing-antibody titers against wild-type virus detected 90% more all on day 29 (geometric mean titer [GMT], 212 354), regardless group, reached 96% by 57 further increase (GMT, 288 488) 1a. Titers remained stable until least 71. provided an factor 2.6 2.9 827 1266). Spike-binding antibody responses similar neutralizing-antibody responses. On 15, CD4+ T-cell 76 83% 60 67% 3, clear skewing toward type helper T cells. CD8+ robust overall but 3.The immunogenicity profiles support development candidate. (Funded Johnson & Biomedical Advanced Research Development Authority Department Health Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.).

Language: Английский

---

Viral targets for vaccines against COVID-19

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(2), P. 73 - 82

Published: Dec. 18, 2020

Language: Английский

---