As of July 16, 2020, the deadly coronavirus (SARS-CoV-2) has infected over 13 million people worldwide and has tragically claimed nearly 600,000 lives. This alarming spread has led many pharmaceutical companies to work tirelessly in search of a vaccine against COVID-19. Amidst the dire news of infections and fatalities, some encouraging updates emerged on July 14, 2020. An interim analysis published in The New England Journal of Medicine described the immune response development in patients participating in the Phase 1 clinical trial for a candidate vaccine created by Moderna, a well-known American biotech firm. The mRNA-1273 vaccine demonstrated a robust immune response, with a reported efficacy of 93.2% in the Phase 3 COVE trial, indicating its potential in reducing symptomatic SARS-CoV-2 infections effectively[1].
Moderna's COVID-19 Vaccine:
Moderna, in collaboration with the US National Institutes of Health (NIH), began developing the mRNA-1273 vaccine candidate even before cases were reported outside of China back in January. Since then, this vaccine has progressed into clinical trials, received significant funding, and has been fast-tracked by the FDA (U.S. Food and Drug Administration). Notably, the mRNA-1273 vaccine has exhibited a favorable safety profile, with the majority of adverse effects being mild and transient, which is consistent with findings from other studies on mRNA vaccines[3].
Vaccine Timeline and Key Milestones:
- January 11, 2020: The genetic sequence of SARS-CoV-2 was shared by Chinese authorities.
- January 13, 2020: The sequence for mRNA-1273 was finalized.
- February 7, 2020: The first clinical batch of mRNA-1273 was completed within 25 days.
- February 24, 2020: The clinical batch was sent to the NIH for Phase 1 clinical study.
- March 4, 2020: The FDA approved the use of the vaccine for clinical trials.
- March 16, 2020: The vaccine was administered to the first participant in the Phase 1 study.
- April 27, 2020: The vaccine was submitted to the FDA for Phase 2 study.
- May 12, 2020: Moderna received FDA fast-track designation for its vaccine.
- May 18, 2020: Positive interim data from the Phase 1 study was announced.
- May 29, 2020: The vaccine was administered to the first participant in the Phase 2 study.
- July 14, 2020: Interim results from the Phase 1 study were published in the NEJM.
Phase 1 Clinical Trials:
In this phase, 45 healthy adults aged between 18 and 55 received two doses of mRNA-1273, spaced 28 days apart. Out of these, 15 adults were administered 25 μg, 15 received 100 μg, and the remaining 15 got 250 μg of the vaccine. The aim of this phase was to determine the effective dosage. Participants who received two doses exhibited high levels of virus-killing antibodies, surpassing the average levels found in recovered COVID-19 patients. This aligns with the findings that mRNA vaccines effectively stimulate a strong humoral response, which is critical for long-term immunity[2].
Phase 1 Results: More than half of the participants experienced mild side effects, such as headaches, fatigue, chills, muscle pain, and soreness at the injection site. Fortunately, no serious side effects requiring hospitalization occurred. It turns out that side effects were more prevalent in those receiving the higher doses, leading the team to choose the 100 μg dose for further studies to reduce adverse reactions, while the 250 μg dose was excluded from Phase 2. This careful dose selection is crucial, especially given the need to balance efficacy with safety[5].
Phase 2 Clinical Trials:
Phase 2 will involve 600 healthy volunteers, both adults aged 18 to 55 and those over 55. Participants will receive either a placebo or doses of 50 μg or 100 μg, administered twice. They will be monitored for 12 months to assess the vaccine's effectiveness in a larger group.
Phase 3 Clinical Trials:
The company plans to kick off the third phase by July 27, 2020. This phase will involve 30,000 volunteers to confirm the vaccine's efficacy and identify any side effects.
Another Promising Vaccine:
A different candidate vaccine (ChAdOx1 nCoV-19) developed by Oxford University aims to stimulate an immune response by delivering a SARS-CoV-2 protein. This vaccine is currently in Phase 3 trials, and results from Phase 1 are yet to be announced.
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References:
- Rolando Pajon, Yamuna D Paila, Bethany Girard, Groves Dixon, Katherine Kacena, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Kathleen M Mullane, Ian Frank, Douglas Denhan, Edward Kerwin, Xiaoping Zhao, Baoyu Ding, Weiping Deng, Joanne E Tomassini, Honghong Zhou, Brett Leav, Florian Schödel. Initial analysis of viral dynamics and circulating viral variants during the mRNA-1273 Phase 3 COVE trial.. PubMed. 2022.
- Sushma Kavikondala, Katrin Haeussler, Xuan Wang, Mary T Bausch-Jurken, Maria Nassim, Nitendra Kumar Mishra, Mia Malmenäs, Pawana Sharma, Nicolas Van de Velde, Nathan Green, Ekkehard Beck. Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework.. PubMed. 2024.
- Gurudeeban Selvaraj, Satyavani Kaliamurthi, Gilles H Peslherbe, Dong-Qing Wei. Are the Allergic Reactions of COVID-19 Vaccines Caused by mRNA Constructs or Nanocarriers? Immunological Insights.. PubMed. 2021.
- Taisei Masuda, Kyoko Murakami, Kenkichi Sugiura, Sho Sakui, Ron Philip Schuring, Mitsuhiro Mori. A phase 1/2 randomised placebo-controlled study of the COVID-19 vaccine mRNA-1273 in healthy Japanese adults: An interim report.. PubMed. 2022.
- Elena Pettini, Annalisa Ciabattini, Gabiria Pastore, Jacopo Polvere, Simone Lucchesi, Fabio Fiorino, Francesca Montagnani, Alessandro Bucalossi, Monica Tozzi, Giuseppe Marotta, Donata Medaglini. A third dose of mRNA-1273 vaccine improves SARS-CoV-2 immunity in HCT recipients with low antibody response after 2 doses.. PubMed. 2022.