Interim results from a phase 3 trial of the Moderna mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine indicated 94% efficacy in preventing coronavirus disease 2019 (Covid-19).¹ The durability of protection is currently unknown. We describe mRNA1273-elicited binding and neutralizing antibodies in 33 healthy adult participants in an ongoing phase 1 trial,^2-4 stratified according to age, at 180 days after the second dose of 100 μg (day 209).

Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. In this phase 1–2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson–Janssen) at a dose of 5×10¹⁰ virus particles, or BNT162b2 (Pfizer–BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.)

The highly transmissible omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of mounting concern globally. The omicron variant carries a large number of spike mutations, including at least 15 mutations in the receptor-binding domain, which is a major target of neutralizing antibodies.¹ To assess the potential susceptibility of this variant to the mRNA-1273 vaccine, neutralization of the omicron variant by serum samples obtained from vaccinated recipients was compared with neutralization of the prototypical D614G variant and the beta (B.1.351) and delta (B.1.617.2) variants. In a pilot study, neutralization of the omicron variant after the primary two-dose regimen of the mRNA-1273 vaccine was lower than that of the D614G and beta variants but increased substantially after a booster dose of the mRNA-1273 vaccine (Figs. S1 through S3 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).

A second wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in India is leading to the emergence of SARS-CoV-2 variants. The B.1.617.1 (or kappa) and B.1.617.2 (or delta) variants were first identified in India and have rapidly spread to several countries throughout the world. These variants contain mutations within the spike protein located in antigenic sites recognized by antibodies with potent neutralizing activity.^1-3 We used serum samples obtained from infected and vaccinated persons to assess neutralizing activity against the SARS-CoV-2 variants in a live-virus assay.

The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our research identifies an excellent system to model SARS-CoV-2 infection of the human airways that can be used to test various treatments. Analysis of infection in this model system found that human airway epithelial cell cultures induce a strong proinflammatory cytokine response yet block the production of type I and III IFNs to SARS-CoV-2. However, treatment of airway cultures with the immune molecules type I or type III interferon (IFN) was able to inhibit SARS-CoV-2 infection. Thus, our model system identified type I or type III IFN as potential antiviral treatments for COVID-19 patients.