- mRNA-1273 is capable of triggering the adaptive immune response. This mRNA essentially codes for the viral spike (S) glycoprotein that is involved in receptor recognition with ACE2 receptors in host cells.
- Uses lipid nanoparticle dispersion that contains mRNA encoding  the stabilized prefusion SARS-CoV-2 spike protein 
- Pre-clinical trials: Rhesus macaque - administration of either 10 or 100 micrograms of the mRNA-1273 showed successful induction of type 1 helper T-cells (Th1)
- In phase 2 of clinical trials and planning on phase 3 later July.
-Supports a two dose (second administration) method of vaccination.

mRNA-1273 COVID-19 Vaccine by ModernaTX, Inc. 

- Lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccines that encode trimerized SARS-CoV-2 spike glycoprotein RBD.
- Currently in Phase 1/2 and testing 3 variations of the vaccines 
- Preliminary report on BNT162b1 available for phase 1/2

BNT162b1/BNT162b2/BNT162b3 Vaccines for COVID-19 by BioNTech/Fosun Pharma/Pfizer

INO-4800 targets the MERS coronavirus Spike protein. The nucleic acid vaccine by attaching to the receptor-binding site and neutralizing the epitopes. The vaccine has initiated a humoral and T-cell response as well as a spike in antibodies which function via competitive inhibition of the ACE2 receptor which the novel coronavirus also binds to. NCT04336410 is optimized through electroporation.

INO-4800 (NCT04336410) by Inovio Pharmaceuticals

This "bacTRL-Spike oral DNA vaccine encoding S of SARS-CoV-2" is under Phase 1 trial.

NCT04334980 by Symvivo

- mRNA-1273 (NCT04405076) Vaccine 
- BNT162b1/BNT162b2/BNT162b3 (NCT04368728) Vaccines
- INO-4800 (NCT04336410) Vaccine
- NCT04334980 Vaccine

Smith College

Carnegie Mellon University

University of California, Santa Cruz

Nucleic Acid Vaccines use genetic material (DNA/RNA) from a viral protein that induces an immune response. The nucleic acid is inserted into human cells, which create copies of the virus protein. For many COVID-19 vaccines in development, the nucleic acid codes for the virus's spike protein. Both DNA and RNA vaccines trigger CD8+ cytotoxic T cell response to eradicate virus, in addition to antibody and CD4+ T cell responses.
However, because of their remarkable risk of failure, not a single nucleic acid vaccine has ever been licensed.

Some types of nucleic acid vaccines include (image):

Nucleic Acid Vaccines for COVID-19

Callaway, E. (2020). The race for coronavirus vaccines: A graphical guide. Nature, 580(7805), 576-577. doi:10.1038/d41586-020-01221-y

https://www.nature.com/articles/d41586-020-01221-y

The race for coronavirus vaccines: a graphical guide

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

https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report

Shin, M.D., Shukla, S., Chung, Y.H. et al. COVID-19 vaccine development and a potential nanomaterial path forward. Nat. Nanotechnol. 15, 646–655 (2020). doi: 10.1038/s41565-020-0737-y

https://doi.org/10.1038/s41565-020-0737-y

COVID-19 vaccine development and a potential
nanomaterial path forward

Nucleic Acid Vaccines in Clinical Trial for COVID-19

Information gained from studies done on both the immune response and vaccine development to related betacoronaviruses can help us gain insight on the immunopathology of SARS-CoV-2 and guide the devlopment of a vaccine. 

Vaccine Development for SARS-CoV-2 Based on Knowledge Gained from SARS-CoV and MERS-CoV

Unlike traditional vaccine, an mRNA vaccine is an mRNA sequence that encodes a specific disease antigen. When the mRNA vaccine enters cells, the antigen gets expressed in the immune system and a strong T-cell response is produced. mRNA vaccines claim to be efficient and less expensive to produce.

mRNA Vaccines for SARS-CoV-2


Nanomaterials have emerged as promising tools to amplify or suppress host's immune response. By acting as adjuvants added to vaccines for COVID-19, engineered nanomaterials can aid subjects with impaired immune system, such as the elderly, and reduce the amount of vaccine protein production and injection. 


Intranasal delivery of polymer-encapsulated antigen triggers a strong immune response, and the success of vaccination depends on the appropriate type of polymer in combination with the antigen. Similarly, researchers have developed lipid and lipid-based NPs as delivery platforms for mRNAs or siRNAs to enable the synthesis of key viral proteins for vaccination (for example, Moderna’s mRNA-1273/NCT04283461 vaccine) or to inactivate critical viral target genes, respectively. 


Considering the possibility of random viral mutations that may alter the antigen shape, functionalizing nanomaterials with a wide number of molecules at the same time to target the virus, or motifs that are specific for pathogens, will increase the efficiency of vaccines and their ability to prevent viral infection.


There are ongoing screenings and classifications of various nanomaterials based on their immunomodulatory properties and cytotoxicity levels. Developing an adjuvant for clinical use requires Phase III randomized trials, which could take several years.


Nanomaterial-based Immune Modulation for SARS-CoV-2

- DNA vaccines have higher stability than mRNA vaccines
- the non-integrating feature of mRNA prevents insertional mutagenesis
- mRNA half-life, stability, and immunogenicity can be modified


DNA vaccines vs RNA vaccines

A self-amplifying RNA (saRNA) vaccine typically consists of a saRNA encapsulated in lipid nanoparticles. This type of vaccine is useful to combat a global pandemic, as it is able to encode any antigen of interest and requires less dosage compared to an mRNA vaccine. 

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