tetano
Editor, Senior Moderator
Nature
. 2020 Aug 12.
doi: 10.1038/s41586-020-2639-4. Online ahead of print.
Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults
Mark J Mulligan[SUP] 1 2 [/SUP], Kirsten E Lyke[SUP] 3 [/SUP], Nicholas Kitchin[SUP] 4 [/SUP], Judith Absalon[SUP] 5 [/SUP], Alejandra Gurtman[SUP] 6 [/SUP], Stephen Lockhart[SUP] 4 [/SUP], Kathleen Neuzil[SUP] 3 [/SUP], Vanessa Raabe[SUP] 1 2 [/SUP], Ruth Bailey[SUP] 4 [/SUP], Kena A Swanson[SUP] 6 [/SUP], Ping Li[SUP] 7 [/SUP], Kenneth Koury[SUP] 6 [/SUP], Warren Kalina[SUP] 6 [/SUP], David Cooper[SUP] 6 [/SUP], Camila Fontes-Garfias[SUP] 8 [/SUP], Pei-Yong Shi[SUP] 8 [/SUP], ?zlem T?reci[SUP] 9 [/SUP], Kristin R Tompkins[SUP] 6 [/SUP], Edward E Walsh[SUP] 10 11 [/SUP], Robert Frenck[SUP] 12 [/SUP], Ann R Falsey[SUP] 10 11 [/SUP], Philip R Dormitzer[SUP] 6 [/SUP], William C Gruber[SUP] 6 [/SUP], Uğur Şahin[SUP] 9 [/SUP], Kathrin U Jansen[SUP] 6 [/SUP]
Affiliations
Abstract
In March 2020, the World Health Organization (WHO) declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[SUP]1[/SUP]. With rapidly accumulating cases and deaths reported globally[SUP]2[/SUP], a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among 45 healthy adults, 18 to 55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 ?g, 30 ?g, or 100 ?g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD). Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 ?g was not administered due to increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared to the 30 μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.9- to 4.6-fold that of a panel of COVID-19 convalescent human sera at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. (ClinicalTrials.gov identifier: NCT04368728).
. 2020 Aug 12.
doi: 10.1038/s41586-020-2639-4. Online ahead of print.
Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults
Mark J Mulligan[SUP] 1 2 [/SUP], Kirsten E Lyke[SUP] 3 [/SUP], Nicholas Kitchin[SUP] 4 [/SUP], Judith Absalon[SUP] 5 [/SUP], Alejandra Gurtman[SUP] 6 [/SUP], Stephen Lockhart[SUP] 4 [/SUP], Kathleen Neuzil[SUP] 3 [/SUP], Vanessa Raabe[SUP] 1 2 [/SUP], Ruth Bailey[SUP] 4 [/SUP], Kena A Swanson[SUP] 6 [/SUP], Ping Li[SUP] 7 [/SUP], Kenneth Koury[SUP] 6 [/SUP], Warren Kalina[SUP] 6 [/SUP], David Cooper[SUP] 6 [/SUP], Camila Fontes-Garfias[SUP] 8 [/SUP], Pei-Yong Shi[SUP] 8 [/SUP], ?zlem T?reci[SUP] 9 [/SUP], Kristin R Tompkins[SUP] 6 [/SUP], Edward E Walsh[SUP] 10 11 [/SUP], Robert Frenck[SUP] 12 [/SUP], Ann R Falsey[SUP] 10 11 [/SUP], Philip R Dormitzer[SUP] 6 [/SUP], William C Gruber[SUP] 6 [/SUP], Uğur Şahin[SUP] 9 [/SUP], Kathrin U Jansen[SUP] 6 [/SUP]
Affiliations
- PMID: 32785213
- DOI: 10.1038/s41586-020-2639-4
Abstract
In March 2020, the World Health Organization (WHO) declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[SUP]1[/SUP]. With rapidly accumulating cases and deaths reported globally[SUP]2[/SUP], a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among 45 healthy adults, 18 to 55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 ?g, 30 ?g, or 100 ?g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD). Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 ?g was not administered due to increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared to the 30 μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.9- to 4.6-fold that of a panel of COVID-19 convalescent human sera at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. (ClinicalTrials.gov identifier: NCT04368728).