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. SARS-CoV-2 vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), but immunogenicity may be reduced in patients undergoing hematopoietic stem cell transplantation (HSCT). The variables that impact the humoral response, such as age, gender, disease and transplant type, prior treatments, and vaccine type, have not been comprehensively described. Methods. A retrospective review was conducted at a single-centre of HSCT recipients who received COVID-19 vaccinations between 2020 and 2021. Participants were included if >18 years and had received at least a single dose of Pfizer, Moderna or Johnson & Johnson (J&J) vaccine. Anti-Spike (S) IgG titers were quantitatively measured at provider discretion during routine care using the Roche Elecsys Anti-SARS-CoV-2 spike immunoassay and categorized as Responders (< 0.8U/mL) and Non-responder (>0.8). Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for Responders vs Non-responders. Controlled risk factors included;Age, disease, treatments, and history of graft-versus-host disease (GVHD). Results. Of 117 HSCT patients assessed, 59 (50.4%) were female, 106 (90.6%) were white, and the median age was 62.5 years (interquartile range [IQR, 49.9-67.8). Vaccinations were administered at a median of 179 days post-transplant (IQR 319 - 105) and antibody responses were measured at a median of 135.5 days post-vaccination (IQR 190-50). 106(90.6%) were responders with a mean titre of 1141.5U/mL (SD=1095.3). 35% had Low (< 100U/mL) titres. Being Female (OR 0.02, 95%CI 0.003 - 0.6) was associated with a slightly higher odds of being a responder. Conclusion. Hematopoietic stem cell transplant recipients demonstrated a high prevalence of anti-S IgG antibody positivity following COVID vaccination. However, neither patient characteristics nor treatment regimens were seen to be strongly associated with anti-S protein positivity among HSCT recipients. More studies are needed to further characterize patient and treatment characteristics that correlate with seroprotection among these patients.