Recent Updates on Moderna COVID-19 Vaccine (mRNA-1273)

Sayan Roy, Pondicherry University

mRNA-1273 is a messenger RNA (mRNA) vaccine, designed to fight against Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). It is developed by a US-based pharmaceutical company- Moderna, in association with NIAID Vaccine Research Center. The mRNA-1273 vaccine encodes for the SARS-CoV-2 full-length spike glycoprotein trimer ‘S-2P’, but modified to incorporate two proline substitutions at amino acid positions 986 and 987, at the top of the central helix in the S2 subunit. This modification has accounted for the vaccine’s defining property of enhanced stability and immunogenicity.

45 volunteers (aged between 18 and 55) were divided into three groups based on the vaccine dosage they received (25μg, 100μg and 250μg, respectively). The groups received their first vaccination between March 16 and April 14, 2020. A total of three volunteers did not receive the second vaccination. The results observed were as follows:

• After the implementation of the first vaccination, mild or moderate systemic adverse events like fatigue, chills, headache, myalgia, and pain at the injection site, were reported by 5,10 and 8 volunteers in the 25-μg group, 100-μg group, and 250-μg group, respectively. There were no reports of fever.
• Solicited systemic adverse events were more common and prominent after the implementation of the second vaccination. Fever was reported in 6 and 8 volunteers in the 100-μg and 250-μg group respectively. And 1 volunteer in the 250-μg group suffered from severe fever.
• High neutralizing antibody responses were elicited in a dose-dependent fashion (assessed by ELISA). 
• The 25-μg and 100-μg doses elicited CD4 T-cell responses. The tumour necrosis factor α (TNF-α) responses were highest, followed by interleukin-2 (IL-2) and interferon-γ (INF-γ) responses, in decreasing order.

In the interim report published on May 18, Moderna announced that mRNA-1273 vaccine was safe and immunogenic. After the initial safety data from the first phase of the study, mRNA-1273 was administered sequentially at the 25-μg dose to the subgroup of volunteers that were between the ages of 56 and 70 years, followed by the administration of the 100-μg dose. After day 8, the 25-μg dose of the vaccine was sequentially administered to the subgroup of volunteers who were 71 years of age or older, followed by the initiation of the 100-μg dose. The observed outcomes were as follows:

• Solicited systemic and local adverse events like headache, fatigue, myalgia, chills, and injection-site pain were reported within 7 days of mRNA-1273 administration. 
• The vaccine elicited a strong CD4 cytokine response involving type 1 helper T (Th1) cells among all the volunteers. The TNF-α responses were highest, followed by IL-2 and INF-γ responses in decreasing order.
• Irrespective of age or dose, the response involving type 2 helper T cells (interleukin-4 and interleukin-13) was minimal.
• After the second vaccination, CD8 T-cell responses were observed only at low levels, amongst volunteers from the two age subgroups that received the 100-μg dose.
• Antibody and T-cell responses observed in this older population (who received the 100-μg dose) were similar to the responses depicted by the participants that had an age range of 18 to 55 years and had also received the 100-μg dose of the vaccine. 

Starting from 27^th July, a broad phase-3 study, with a more diverse population was launched to evaluate the safety and effectiveness of the vaccine against the virus, to assess and define its level of protection against the activity of SARS-CoV-2.

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References: 

1. Anderson, E. J., Rouphael, N. G., Widge, A. T., Jackson, L. A., Roberts, P. C., Makhene, M., … Beigel, J. H. (2020). Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. New England Journal of Medicine. DOI:10.1056/nejmoa2028436
2. Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., … Beigel, J. H. (2020). An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. New England Journal of Medicine. DOI:10.1056/nejmoa2022483
3. https://uk.reuters.com/article/us-health-coronavirus-moderna/moderna-covid-19-vaccine-appears-safe-shows-signs-of-working-in-older-adults-study-idUKKBN26K3KE
4.   https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19

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