The global effort to combat COVID-19 has spurred the rapid development and deployment of various vaccine platforms, including mRNA and DNA vaccines. These vaccines have shown varying degrees of efficacy and safety, playing a crucial role in mitigating the pandemic's impact. This article reviews the current landscape of COVID-19 vaccines, focusing on mRNA and DNA-based approaches.
mRNA Vaccines: Efficacy and Variant Response
mRNA vaccines, such as Pfizer-BioNTech's BNT162b2 and Moderna's mRNA-1273, have been at the forefront of the global vaccination campaign. These vaccines utilize genetically engineered mRNA to instruct host cells to produce viral proteins, stimulating an immune response. Clinical trials have demonstrated high efficacy, ranging from 72% to 95%, against moderate-to-severe COVID-19 in adults.
A study by Polack et al. investigated the safety and effectiveness of the BNT162b2 vaccine, revealing a 95% protection rate against COVID-19 in individuals aged 16 years and above. Common side effects included mild-to-moderate pain at the injection site, fatigue, and headache. Similarly, the Moderna mRNA-1273 vaccine showed 94.1% efficacy in preventing COVID-19 and severe disease in a phase III trial conducted in the United States.
However, the emergence of SARS-CoV-2 variants has posed challenges to vaccine efficacy. Stamatatos et al. (2021) found that while pre-immunization sera from recovered individuals could neutralize the Wuhan-Hu-1 strain, its effectiveness against the B.1.351 variant was limited. Vaccination with BNT162b2 and mRNA-1273 significantly increased antibody titers against both variants, highlighting the importance of vaccination in both previously infected and naive populations.
Narowski et al. investigated the immunogenic activity induced by the Pfizer-BioNTech and Moderna vaccines against various SARS-CoV-2 variants. The study found weaker immune reactions against the Alpha and Delta variants compared to the reference strain, suggesting the need for custom-made vaccines against evolving variants. Studies have also shown that a third dose of mRNA vaccine BNT162b2 increases immune response against the Omicron variant by 23-fold compared to the level after the second dose.
DNA Vaccines: A Promising Alternative
DNA vaccines represent another approach to COVID-19 immunization. These vaccines use plasmids containing DNA sequences encoding viral antigens to stimulate an immune response. While fewer DNA vaccines have reached advanced stages of clinical development compared to mRNA vaccines, they offer potential advantages in terms of cost-effectiveness and ease of storage.
Zydus Cadila, in collaboration with the Department of Biotechnology, India, developed ZyCov-D, a three-dose intradermal DNA vaccine approved for individuals aged 12 years and above. A phase III clinical trial conducted at 49 sites in India demonstrated a 66.6% efficacy rate, with a good safety profile and the ability to induce neutralizing antibodies and cellular immune responses. The company reported no severity and mortality in phase I trial.
INOVIO's INO-4800 is another DNA-based vaccine administered intradermally with electroporation. Phase III trials are underway, with earlier studies showing satisfactory immune responses against SARS-CoV-2 variants and good tolerability in young and elderly individuals.
Dose Interval and Immune Response
Several studies have investigated the impact of dose interval on the effectiveness of mRNA vaccines. Research suggests that extending the interval between the first and second doses of BNT162b2 may enhance immune responses, particularly in previously uninfected individuals. A study found that distantly administered doses produced stronger responses, suggesting improved efficacy and greater flexibility in vaccination schedules. However, the recognition of variants like Omicron was found to decline more rapidly among naive individuals compared to previously infected individuals.
Conclusion
The COVID-19 vaccine landscape continues to evolve, with mRNA and DNA vaccines playing critical roles in controlling the pandemic. While mRNA vaccines have demonstrated high efficacy and have been widely deployed, DNA vaccines offer a promising alternative, particularly in resource-limited settings. Ongoing research is focused on optimizing vaccine formulations, addressing emerging variants, and refining vaccination strategies to achieve broader and more durable immunity.
