COVID-19 research briefs: Promising preliminary data on COVID-19 vaccines from the United States and United Kingdom

Clinical question
What is the progress on the development of a vaccine against SARS-CoV-2?

Bottom line
There is promising early data from the United States and the United Kingdom on new vaccines to prevent COVID-19. (LOE = 3b)

Reference
Jackson LA, Anderson EJ, Rouphael NG, et al, for the mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2 — preliminary report. N Engl J Med. Published online July 14, 2020. doi: 10.1056/NEJMoa2022483

Study design: Not applicable

Funding source: Unknown/not stated

Setting: Population-based

Synopsis
Research Brief #47: Around the world, more than 100 candidate vaccines against SARS-CoV-2 are in various stages of development and testing. This report is of an open-label open-label Phase I trial of 45 healthy adults. The participants received 2 doses of 25 μg, 100 μg, or 250 μg, 4 weeks apart, of Moderna's messenger RNA vaccine (mRNA-1273). There was no comparison group, and the researchers did not screen the participants for SARS-CoV-2 infection by serology or polymerase chain reaction before enrollment (a significant limitation). The study protocol called for assessments at multiple points after each vaccination, including on days 7, 14, 57, 119, 209, and 394 (okay, where do they come up with some of these intervals?). On days 1, 15, 29, 36, 43, and 57, the researchers tested each participant for binding antibodies and for neutralizing activity. Three of the 45 participants did not receive the second vaccination, one of whom developed urticaria and one who was in isolation for suspected COVID-19. On day 57, the researchers were able to detect binding and neutralizing antibodies with all 3 doses of mRNA-1273 by 14 days after immunization, with a peak at 28 days. The high-dose vaccine induced the greatest immunogenic response, but also the highest rate of adverse effects. Additionally, as we have observed with the new recombinant zoster vaccine, the second vaccine triggers more frequent adverse events: 54%, 100%, and 100% for each of the 3 doses, respectively. Fortunately, most of these were considered mild and only 3 participants who received the highest dose reported one or more serious adverse effects (21%). The adverse events included fever, arthralgias, injection site pain, headache, chills. These are early and incomplete data from a small study with no control group, but provides hope that an effective vaccination is feasible. Jackson LA, Anderson EJ, Rouphael NG, et al, for the mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2 — preliminary report. N Engl J Med. Published online July 14, 2020. doi: 10.1056/NEJMoa2022483 Research Brief #48: There have been 2 very small vaccine trials with 108 participants and 45 participants) with promising results. This is by far the largest study to date. These researchers randomized more than 1000 healthy adults in the United Kingdom to receive a single intramuscular dose of either Oxford University's chimpanzee adenovirus-vectored vaccine (at a dose of 5 x 1010 viral particles) that targets the spike protein (n = 543) or a meningococcal vaccine (n = 534). The team used an active comparator vaccine because of known local and systemic reactions that are likely to be less apparent with a simple saline placebo vaccine. The participants had no laboratory evidence of SARS-CoV-2 infection, no COVID-19 symptoms, and could not be at high risk of exposure. The staff who administered the vaccines, the investigators, and the laboratory teams were all masked to which vaccine the participants received. To illustrate some of the complexities involved with vaccine trials, the researchers divided the participants into 4 distinct study groups. They evaluated group 1 participants for safety and immunogenicity at 3, 7, 14, 28, and 56 days after vaccination. The researchers took greater volumes of blood from group 2 participants to allow for assessing humoral and cellular immunogenicity. Group 3 included 10 participants who received a booster dose 28 days after the first dose. Group 4 participants were evaluated only for humoral immune response. Approximately 10% of participants in each group took prophylactic paracetamol (acetaminophen). The rate of fatigue was the same whether or not the participant took paracetamol (70% vs 71%), but headaches were slightly less common in those who took paracetamol (68% vs 61%). Other common reactions included myalgias, malaise, chills, and feverishness, most of which were also slightly less common in those who took paracetamol. Two weeks later, those who received the active vaccine already had T-cell responses, and by 4 weeks also had an antibody response: 91% had neutralizing antibodies. All participants who received the booster developed neutralizing antibodies. The report doesn't say what proportion of patients developed cellular immunity. These results move us a little closer to having a safe, effective vaccine. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. Published online July 20, 2020. doi: 10.1016/s0140-6736(20)31604-4.

Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI

Copyright © 2020 John Wiley & Sons, Inc.