The race to develop an effective vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on, and one of the potential candidates shows promise in inducing an immune response.
The US biotech firm Moderna announced it would enter the final stage of its human trials for the coronavirus disease (COVID-19) vaccine on July 27, after revealing the promising results of its open-label phase 1 study. The vaccine, called mRNA-1273, is the firm’s candidate vaccine against SARS-CoV-2 infection.
The early results of the trial, published in the New England Journal of Medicine (NEJM), revealed that the vaccine triggered an immune response with mild side effects, including chills, fatigue, headache, muscle pain, and injection site pain. It is the first vaccine candidate of the United States to publish its results in a peer-reviewed journal.
The results from the participants in the initial dose who received both vaccinations were validated and revealed that the vaccine-induced rapid and robust immune responses against the novel coronavirus.
Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
The vaccine candidate, mRNA-1273, is an mRNA vaccine against SARS-CoV-2 encoding for a prefusion stabilized form of the spike protein. Moderna collaborated with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID) to develop the vaccine.
The first clinical batch of the vaccine was funded by the Coalition for Epidemic Preparedness Innovations (CEPI).
The clinical trial
The first phase of the human clinical trial involved 45 healthy adults between 18 and 55 years old, who received two doses of the vaccine, ranging from 25 μg, 100 μg, or 250 μg, 28 days apart. Each of the dose group had 15 participants.
The team found that after the first vaccination, antibody responses were higher with a higher dose. The candidate vaccine induced binding antibodies to the full-length SARS-CoV-2 spike protein (S) in all participants after the first vaccination. All the participants seroconverted by the 15th day. Further, dose-dependent increases in binding titers were observed at all three dose levels.
At day 57, geometric mean titers surpassed those seen in convalescent sera extracted from 38 people who were confirmed to have COVID-19. Of these, 15 percent ha severe symptoms, 22 percent had moderate symptoms, and 63 percent had only mild symptoms.
The team analyzed the neutralizing activity in two assays, the PRNT or the SARS-CoV-2 plaque-reduction neutralization test and a pseudovirus neutralization assay or pseudotyped lentivirus reporter single-round-of-infection neutralization assay (PsVNA).
After two doses of vaccinations, the Moderna vaccine-induced potent neutralizing antibody titers and by the 43rd day, the neutralizing activity against the SARS-CoV-2 was observed in all the participants. T cell responses were also seen at the 25 µg and 100 µg doses. After the second dosage, the mRNA1273 Th1-biased CD4 T-cell responses without significant evaluation of Th2-biased CD4 T- cell responses.
“The mRNA-1273 vaccine-induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine,” the researchers concluded.
The researchers added that safety and immunogenicity findings suggest that the vaccine should advance to later-stage human trials.
Currently, the phase 2 trial of mRNA-1273 in 600 healthy adults, which evaluates the doses of 50 μg and 100 μg, is ongoing. The company also announced that after the phase 2 trial ends, it plans to conduct the phase 3 trial that will commence this summer.
“These positive Phase 1 data are encouraging and represent an important step forward in the clinical development of mRNA-1273, our vaccine candidate against COVID-19, and we thank the NIH for their ongoing collaboration. The Moderna team continues to focus on starting our Phase 3 study this month and, if successful, filing a BLA,” Stéphane Bancel, Chief Executive Officer of Moderna, said in a news release.
“We are committed to advancing the clinical development of mRNA-1273 as quickly and safely as possible while investing to scale up manufacturing so that we can help address this global health emergency,” she added.
Meanwhile, Moderna’s stock skyrocketed by 17 percent on July 14 after the firm announced its candidate vaccine against COVID-19 produced robust immune system response.
The coronavirus pandemic is still actively spreading across the globe, with the infection toll now reaching more than 13.49 million. With the increasing number of confirmed cases and deaths, finding an effective vaccine is a race against time.