An RNA vaccine candidate, BNT162b1, is shown to induce a robust immune response in healthy adults aged 18–55 years in an interim report of a phase 1/2 clinical trial. RNA vaccine platforms, which use messenger RNA to elicit an immune response, are generally considered safe and have facilitated the rapid development of vaccines against SARS-CoV-2.
Delivered intramuscularly, BNT162b1, which encodes a SARS-CoV-2 receptor-binding domain antigen, is one of several RNA vaccine candidates that are being studied in parallel for selection to advance to a trial of their safety and efficacy.
Judith Absalon and colleagues at New York University Langone Vaccine Centre, New York University Grossman School of Medicine and Vaccine Research and Development at Pfizer Inc, report interim data from an ongoing phase 1/2 clinical study of BNT162b1. Forty-five healthy adults (23 men and 22 non-pregnant women; 37 participants were white) aged 18–55 years were randomized to receive 10 micrograms (μg), 30 μg or 100 μg of BNT162b1, or a placebo. Participants in the 10-μg and 30- μg groups also received a second dose on day 21.
The authors found that BNT162b1 was generally well-tolerated, although some participants experienced mild to moderate side effects, which increased with dose level, in the seven days following vaccination, including pain at the injection site, fatigue, headache, fever and sleep disturbance.
The vaccine elicited a robust immune response in participants, which increased with dose level and with a second dose. Antibodies against SARS-CoV-2 were present 21 days after a single vaccination at all dose levels, and there was a substantial increase in SARS-CoV-2-neutralising antibodies 7 days after the second 10-μg or 30-μg dose was given. The immune response was much stronger in the 30-μg group than in the 10-μg group.
However, there were no notable differences in immune response between the 30-μg and 100-μg groups after one dose, and as participants who received the 100-μg dose also experienced greater side effects, they did not receive a second dose.
Participants’ levels of neutralizing antibodies were 1.9 to 4.6 times higher than those in patients recovering from SARS-CoV-2 infection. However, although this comparison provides a benchmark for evaluating the vaccine-elicited immune response and the vaccine’s potential to provide protection, phase 3 trials are needed to determine the efficacy of BNT162b1. The study is also enrolling adults aged 65–85 years, and later phases will prioritize the enrolment of more-diverse populations.
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)1. With rapidly accumulating cases and deaths reported globally2, 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 µg, 30 µg, or 100 µg 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 µg 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.
Authors
Mark J Mulligan, Kirsten E Lyke, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, Kathleen Neuzil, Vanessa Raabe, Ruth Bailey, Kena A Swanson, Ping Li, Kenneth Koury, Warren Kalina, David Cooper, Camila Fontes-Garfias, Pei-Yong Shi, Özlem Türeci, Kristin R Tompkins, Edward E Walsh, Robert Frenck, Ann R Falsey, Philip R Dormitzer, William C Gruber, Uğur Şahin, Kathrin U Jansen
[link url="https://www.nature.com/articles/s41586-020-2639-4"]Nature abstract[/link]