Reactogenicity, Safety, and Serological and Cellular Immunogenicity of a Booster Dose of SARS-CoV-2 mRNA Prototype, Variant, and Bivalent Vaccines (preprint)

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for booster doses. We evaluated safety and serological and cellular immunogenicity through 6 months after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, Delta and Omicron variants that persisted through 6 months post-boost, particularly after administration of Beta-containing vaccines. Spike-specific CD4 + and CD8 + T cells increased to levels similar to those following the second dose. Boost vaccination induced broad and durable humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine — An Interim Analysis (preprint)

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for a third dose of vaccine. We evaluated early safety and immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, and Delta variants that were similar or greater than peak responses after the second dose. Spike-specific CD4+ and CD8+ T cells increased to similar levels as after the second dose. A third mRNA vaccination was well tolerated and generated robust humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

Seroprevalence of SARS-CoV-2 Infection in Cincinnati Ohio USA from August to December 2020 (preprint)

The world is currently in a pandemic of COVID-19 (Coronavirus disease-2019) caused by a novel positive-sense, single-stranded RNA {beta}-coronavirus referred to as SARS-CoV-2. Fortunately, most infected individuals recover and are then resistant to re-infection for a period, indicating that a vaccination approach can be successful. Elucidation of rates of past SARS-CoV-2 infection within select regions across the United States of America (USA) will help direct vaccination efforts and together will inform our approach towards achieving herd immunity. Here we investigated rates of SARS-CoV-2 infection in the greater Cincinnati, Ohio, USA metropolitan area from August to December 2020, just prior to initiation of the national vaccination program. Examination of 9,550 adult blood donor volunteers for serum IgG antibody positivity against the SARS-CoV-2 Spike protein showed an overall prevalence of 8.40%, measured as 7.56% in the first 58 days of this time frame, versus a significant increase to 9.24% in the last 58 days, and a final rate of 12.86% in December 2020. Approximately 56% of Spike seropositive individuals also had immunoreactivity against the receptor binding domain (RBD) within the Spike protein, which is associated with viral neutralization. Males and females in the Cincinnati area showed nearly identical rates of past infection, and rates among Hispanics, African Americans and Caucasians were not significantly different. Interestingly, donors under 30 years of age had the highest rates of past infection, while those over 60 had the lowest. Geographic analysis showed that the West side of Cincinnati had a rate of 9.63% versus 8.13% on the East side (demarcated by Interstate-75), while the adjoining area of Kentucky was 7.04% (as demarcated by the Ohio River). These results among healthy blood donors will be critical in calculating the time needed to achieve regional herd immunity in conjunction with the national vaccination campaign.