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Preliminary mRNA Vaccine Against SARS-CoV-2
Quick Takes
- A vaccine based on mRNA encoding SARS-CoV-2 spike glycoprotein appears to be immunogenic and safe in the population studies.
- The vaccine was tested in younger individuals. Whether it is immunogenic in higher-risk populations such as the elderly and translates to clinical efficacy is unclear.
- The rapid development of the vaccine represents a technological and scientific feat that may change our approach to future pandemics.
Study Questions:
Is the vaccine based on mRNA encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein safe and immunogenic?
Methods:
The authors conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18-55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. Patients were not screened for SARS-CoV-2 infection prior to enrollment. The candidate vaccine mRNA-1273 is a lipid nanoparticle–encapsulated, nucleoside-modified messenger RNA (mRNA)-based vaccine that encodes the SARS-CoV-2 spike (S) glycoprotein. The vaccine was co-developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID, the trial sponsor) and at Moderna (Cambridge, MA).
Participants recorded local and systemic reactions, using a memory aid, for 7 days after each vaccination. Binding antibody responses against the spike glycoprotein were assessed by enzyme-linked immunosorbent assay (ELISA), and vaccine-induced neutralizing activity was assessed in vitro at days 1, 15, 29, 36, 43 and 57. T-cell responses against spike protein were also assessed using intracellular cytokine-staining. The participants’ immune responses were compared to those induced by SARS-CoV-2 infection using 41 convalescent serum specimens. This interim study reported follow-up up to 57 days.
Results:
Of 45 enrolled participants, 22 (49%) were men and 40 (89%) were white. The mean age was 33 years. Three participants did not receive the second vaccine: two due to urticaria after the first vaccination and one missed the window of vaccination. There were no severe adverse events. There was, however, a step-wise increase in systemic symptoms with increasing vaccine dose, and a higher frequency of symptoms after the second vaccination. The most common symptoms were fatigue, headache, myalgia, and chills. The vaccine elicited SARS-CoV-2 antibody responses in a dose-dependent fashion, with magnitudes similar to that observed in convalescent serum specimens even after the first vaccination. However, less than half of the participants exhibited serum neutralizing activity after the first dose. All participants, however, had neutralizing responses after the second dose. Antibody responses and neutralizing activity correlated. With regard to T-cell responses, type 1 helper T-cell response was predominant (tumor necrosis factor-alpha, interleukin-2, interferon gamma).
Conclusions:
The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, without severe adverse effects.
Perspective:
Development of this vaccine using the mRNA platform was a remarkable feat. Processes that typically take years to complete were achieved in 2 months, leading to the current vaccine trial, for which interim results for safety and immunogenicity are promising. Should the vaccine prove to be effective in phase 3 trials, similar processes will be adopted for the inevitable future pandemics to mitigate their impact. There is still much work to be done. The study was performed in younger individuals, and it is unclear whether higher-risk patient populations such as the elderly will show a similar immunogenic response with the frequency and doses administered in this trial. Whether the immunogenic responses translate to clinical efficacy will need to be assessed in a phase 3 trial, which will likely require thousands of participants and be complicated by the fluid nature of the pandemic. Diligence and cautious optimism define the path forward.
Clinical Topics: COVID-19 Hub, Prevention
Keywords: Antibodies, Chills, COVID-19, Headache, Interleukins, Myalgia, Primary Prevention, RNA, Messenger, SARS Virus, severe acute respiratory syndrome coronavirus 2, Urticaria, Vaccination
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