New England Journal of Medicine

BackgroundBooster doses of COVID-19 vaccines help restore protection against waning immunity and emerging variants. Having found that fractional BNT162b2 boosters were non-inferior to standard boosters in eliciting anti-spike IgG responses at day 28 in Mongolian adults, we assessed long-term immunogenicity and safety in the same cohort. MethodsIn this randomised, controlled, non-inferiority trial, adults previously vaccinated with two doses of ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were random...

BACKGROUNDQatar has been experiencing a large SARS-CoV-2 Omicron (B.1.1.529) wave that started on December 19, 2021. We assessed duration of protection of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines after second dose and after third/booster dose against symptomatic Omicron infection and against COVID-19 hospitalization and death, between December 23, 2021 and February 2, 2022. METHODSVaccine effectiveness was estimated using the test-negative, case-control study design,...

BackgroundThe safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported. MethodsWe conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to rece...

Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk a...

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available. MethodsHealthy adults 18-55 and 65-85 years of age were randomized in an ongoing, placebo-controlled, observer-blinded dose-escalation study to receive 2 doses at 21-day intervals of placebo or either of 2 lipid nanopar...

BackgroundSubvariants of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron XBB-lineage have the potential to escape immunity provided by prior infection or vaccination. For Covid-19 immunizations beginning in the Fall 2023, the U.S. FDA has recommended updating to a monovalent omicron XBB.1.5-containing vaccine. MethodsIn this ongoing, phase 2/3 study participants were randomized 1:1 to receive 50-{micro}g doses of mRNA-1273.815 monovalent (50-{micro}g omicron XBB.1.5 spike...

BackgroundProtection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. MethodsSix national, matched, test-negative, case-control studies were conducted between January 18-December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. ResultsEffectiven...

BackgroundDespite the availability of effective vaccines against coronavirus disease 2019 (Covid-19), the emergence of variant strains and breakthrough infections pose a challenging new reality. Booster vaccinations are needed to maintain vaccine-induced protection. MethodsENSEMBLE2 is an ongoing, randomized, double-blind, placebo-controlled, phase 3 pivotal trial including crossover vaccination after emergency authorization of Covid-19 vaccines. Adults aged [≥]18 years were randomized to re...

BackgroundBooster vaccines providing protection against emergent SARS-CoV-2 variants are needed. In an international phase 3 study, we evaluated booster vaccines containing prototype (D614) and/or Beta (B.1.351) variant recombinant spike proteins and AS03 adjuvant (CoV2 preS dTM-AS03). MethodsAdults, primed 4-10 months earlier with mRNA (BNT162b2, mRNA-1273]), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or adjuvanted protein (CoV2 preS dTM-AS03 [D614]) vaccines and stratified by age (18-5...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic of coronavirus disease 2019 (COVID-19) that has led to more than 3 million deaths worldwide. Safe and effective vaccines are now available, including the mRNA-1273 prototype vaccine, which encodes for the Wuhan SARS-CoV-2 spike (S) protein stabilized in the prefusion conformation by 2 proline substitutions. This vaccine showed 94% efficacy in prevention of symptomatic COVID-19 disease in a ph...

BackgroundInformation on the safety and immunogenicity of the omicron BA.4/BA.5-containing bivalent booster mRNA-1273.222 are needed. MethodsIn this ongoing, phase 2/3 trial, 50-g mRNA-1273.222 (25-g each ancestral Wuhan-Hu-1 and omicron BA.4/BA.5 spike mRNAs) is compared to 50-g mRNA-1273, administered as second boosters in adults who previously received a 2-injection (100-g) primary series and first booster (50-g) dose of mRNA-1273. The primary objectives were safety and immunogenicity 28 day...

BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [≥]65 and those aged 12-64 years at high-risk of severe COVID-19. MethodsData were generated from: (1) two independent, ongoing, phase 3b/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA...

In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 g, 30 g,...

BackgroundNVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. MethodsThis is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and imm...

BackgroundLong-term effectiveness of COVID-19 mRNA boosters in populations with different prior infection histories and clinical vulnerability profiles is inadequately understood. MethodsA national, matched, retrospective, target trial cohort study was conducted in Qatar to investigate effectiveness of a third mRNA (booster) dose, relative to a primary series of two doses, against SARS-CoV-2 omicron infection and against severe COVID-19. Associations were estimated using Cox proportional-hazard...

BackgroundEffective COVID-19 mRNA vaccines are mainly available in high-income countries. ChulaCov19, a prefusion non-stabilized Spike protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine development, aims to enhance accessibility of mRNA vaccine and future pandemic preparedness for low- to middle-income countries. MethodsSeventy-two eligible volunteers, 36 aged 18-55 (adults) followed by 36 aged 56-75 (elderly) enrolled in a dose escalation study of ChulaCov19 mR...

As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming followed by boosting with 100-g or 50-g mRNA-1273, Ad26.COV2.S single-dose priming followed by Ad26.COV2.S booster and BNT162b2 two-dose priming followed...

BackgroundTo combat the SARS-CoV-2 pandemic, multiple vaccines using different manufacturing platforms have been developed, including NVX-CoV2373 (an adjuvanted recombinant protein vaccine). As SARS-CoV-2 variants have emerged, some of which evade vaccine-induced immunity, introduction of vaccine booster doses has become critical. Employing different vaccine types for primary series vaccination and boosting could expand vaccine coverage and access. This study assessed whether NVX-CoV2373 would i...

BackgroundThe emergence of SARS-CoV-2 variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5{micro}g SARS-CoV-2 rS + 50{micro}g Matrix-M adjuvant) was evaluated to determine induction of cross-reactive antibodies to variants of concern. MethodsA phase 2 randomized study assessed a fourth dose of NVX-CoV2373 in adults 18-84 years of age (2-dose primary series followed by third and fourth doses at 6-month intervals). Local/systemic reactogenicit...

BackgroundWe report the clinical efficacy against COVID-19 infection of BBV152, a whole-virion inactivated SARS-CoV-2 vaccine formulated with a Toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG). MethodsWe did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18-98 years) randomised 1:1 using a computer-generated randomisation scheme received...