tetano
Editor, Senior Moderator
Nat Med
. 2022 Oct 6.
doi: 10.1038/s41591-022-02031-7. Online ahead of print.
Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial
Spyros Chalkias[SUP] 1 [/SUP], Frank Eder[SUP] 2 [/SUP], Brandon Essink[SUP] 3 [/SUP], Shishir Khetan[SUP] 4 [/SUP], Biliana Nestorova[SUP] 5 [/SUP], Jing Feng[SUP] 5 [/SUP], Xing Chen[SUP] 5 [/SUP], Ying Chang[SUP] 5 [/SUP], Honghong Zhou[SUP] 5 [/SUP], David Montefiori[SUP] 6 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Bethany Girard[SUP] 5 [/SUP], Rolando Pajon[SUP] 5 [/SUP], Frank J Dutko[SUP] 5 [/SUP], Brett Leav[SUP] 5 [/SUP], Stephen R Walsh[SUP] 7 [/SUP], Lindsey R Baden[SUP] 7 [/SUP], Jacqueline M Miller[SUP] 5 [/SUP], Rituparna Das[SUP] 5 [/SUP]
Affiliations
Abstract
Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series ( NCT04927065 ). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-µg primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-µg booster. The mRNA-1273.211 booster doses (50-µg or 100-µg) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA‑1273 dose of the primary series ( NCT04470427 ). Antibody responses 28 days and 180 days after the 50-µg mRNA-1273.211 booster dose were also higher than those after a 50-µg mRNA-1273 booster dose ( NCT04405076 ) against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-µg) was similar to the booster dose of mRNA-1273 (50-µg). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.
. 2022 Oct 6.
doi: 10.1038/s41591-022-02031-7. Online ahead of print.
Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial
Spyros Chalkias[SUP] 1 [/SUP], Frank Eder[SUP] 2 [/SUP], Brandon Essink[SUP] 3 [/SUP], Shishir Khetan[SUP] 4 [/SUP], Biliana Nestorova[SUP] 5 [/SUP], Jing Feng[SUP] 5 [/SUP], Xing Chen[SUP] 5 [/SUP], Ying Chang[SUP] 5 [/SUP], Honghong Zhou[SUP] 5 [/SUP], David Montefiori[SUP] 6 [/SUP], Darin K Edwards[SUP] 5 [/SUP], Bethany Girard[SUP] 5 [/SUP], Rolando Pajon[SUP] 5 [/SUP], Frank J Dutko[SUP] 5 [/SUP], Brett Leav[SUP] 5 [/SUP], Stephen R Walsh[SUP] 7 [/SUP], Lindsey R Baden[SUP] 7 [/SUP], Jacqueline M Miller[SUP] 5 [/SUP], Rituparna Das[SUP] 5 [/SUP]
Affiliations
- PMID: 36202997
- DOI: 10.1038/s41591-022-02031-7
Abstract
Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of the bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding the ancestral SARS-CoV-2 and Beta variant spike proteins, as 50-µg (n = 300) and 100-µg (n = 595) first booster doses administered approximately 8.7-9.7 months after the mRNA-1273 primary vaccine series ( NCT04927065 ). The primary objectives were to evaluate the safety and reactogenicity of mRNA-1273.211 and to demonstrate non-inferior antibody responses compared to the mRNA-1273 100-µg primary series. Additionally, a pre-specified immunogenicity objective was to demonstrate superior antibody responses compared to the previously authorized mRNA-1273 50-µg booster. The mRNA-1273.211 booster doses (50-µg or 100-µg) 28 days after immunization elicited higher neutralizing antibody responses against the ancestral SARS-CoV-2 and Beta variant than those elicited 28 days after the second mRNA‑1273 dose of the primary series ( NCT04470427 ). Antibody responses 28 days and 180 days after the 50-µg mRNA-1273.211 booster dose were also higher than those after a 50-µg mRNA-1273 booster dose ( NCT04405076 ) against the ancestral SARS-CoV-2 and Beta, Omicron BA.1 and Delta variants, and all pre-specified immunogenicity objectives were met. The safety and reactogenicity profile of the bivalent mRNA-1273.211 booster (50-µg) was similar to the booster dose of mRNA-1273 (50-µg). Immunization with the primary series does not set a ceiling to the neutralizing antibody response, and a booster dose of the bivalent vaccine elicits a robust response with titers that are likely to be protective against COVID-19. These results indicate that bivalent booster vaccines can induce potent, durable and broad antibody responses against multiple variants, providing a new tool in response to emerging variants.