ABSTRACT
Background. Vaccination strategies that provide enhanced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are needed. We evaluated the safety and immunogenicity of a bivalent omicron containing vaccine, mRNA-1273.214 (50 mug), administered as a second booster dose in adult participants. Methods. In this ongoing phase 2/3 trial, 50 mug of the bivalent vaccine mRNA-1273.214 (25 mug each ancestral Wuhan-Hu-1 and omicron BA.1 spike mRNAs) or 50 mug of the authorized mRNA-1273 were administered as second boosters in adults who previously received a 2 dose (100 mug) primary series and a first booster (50 mug) dose of mRNA-1273 (>= 3 months prior). Primary objectives were safety and reactogenicity and immunogenicity 28 days post-booster dose. Results. In participants with no prior SARS-CoV-2 infection who received booster doses of mRNA-1273.214 (n=334) or mRNA-1273 (n=260), neutralizing antibody (nAb) geometric mean titers (GMTs [95% confidence interval (CI)]) against omicron BA.1 were 2372.4 (2070.6-2718.2) and 1473.5 (1270.8-1708.4), respectively. The model-based GMT ratio (GMR [97.5% CI]) of mRNA-1273.214 compared to mRNA-1273 was 1.75 (1.49-2.04), meeting the pre-specified superiority criterion against omicron BA.1. The pre-specified criterion for non-inferiority against the ancestral SARS-CoV-2 strain was also met. Additionally, mRNA-1273.214 elicited higher GMTs (727.4 [632.8-836.1]) than mRNA-1273 (492.1 [431.1-561.9]) against omicron subvariants BA.4/BA.5 [GMR (95% CI) 1.69 [1.51-1.90])]. Binding antibody responses against alpha, beta, gamma, delta, and omicron were numerically higher in the mRNA-1273.214 group compared to mRNA-1273. mRNA-1273.214 GMTs were consistently higher across age (18-< 65 and >= 65 years) and pre-booster SARS-CoV-2 infection subgroups (Figure). Safety and reactogenicity were similar for both vaccine groups. Conclusion. The bivalent omicron containing mRNA-1273.214 elicited superior nAb responses against omicron 28 days post-immunization compared to mRNA-1273 regardless of age and prior SARS-CoV-2 infection;no new safety concerns were identified. (Figure Presented).
ABSTRACT
Background. Two years into the pandemic, clinicians do not have access to a standardized measurement of SARS-CoV-2 viral load (VL) that allows for VL comparison across clinical specimens and different assays. Reliable VL measurement in diverse respiratory specimens, over time, and in response to treatments such as remdesivir (RDV), could better inform treatment and prevention. Methods. To investigate the use of a standardized VL assay in respiratory specimens, we enrolled patients hospitalized with COVID-19 in Providence, RI, with/ without RDV exposure;collected serial samples from 4 compartments (nasopharyngeal-NP, nasal-NA, oropharyngeal-OP, saliva-SA) in 3 visits during the 1st week of hospitalization;and characterized SARS-CoV-2 VL using a ChromaCode HDPCRTM quantitative research use only assay, calibrated to the first World Health Organization (WHO) International Standard (IS). Linear mixed effects models and associated regression coefficients were used to analyze intercompartmental VL differences at enrollment, over time, and with/without RDV. Results. Of 35 participants (60% male;70% White, 14% Hispanic/Latino, 49% RDV exposure), all had visit 1 samples (median hospital day 1, IQR 0-2;pre-RDV for those exposed);80% visit 2 samples (median hospital day 2, IQR 1-8);and 37% visit 3 samples (median hospital day 4, IQR 3-7). Overall, 38 NP, 67 NA, 57 OP, and 67 SA samples were collected. Mean log VLs (Log10IU/mL) differed by compartment at visit 1 (NP 6.3, NA 4.9, OP 4.1, SA 5.6, p=0.0001) and significantly decreased over time in all compartments (p< 0.04 for all comparisons). Log VL change over time was not significantly different between compartments or between people treated/not treated with RDV. Conclusion. We successfully measured respiratory intercompartmental SARS-CoV-2 VL differences among hospitalized patients using a standardized assay calibrated to the WHO IS. Dissemination of standardized VL measurement methods will allow accurate VL comparisons across assay types quantified in IU/mL and improve assessment of the impact of COVID-19 treatments. Inter-compartmental VL differences at baseline may indicate sampling variability or different viral burden. RDV did not appear to accelerate viral decay.