A self-amplifying RNA encoding a spike protein of SARS-CoV-2 encapsulated in a lipid nanoparticle vaccine was studied in mice as a potential vaccine candidate to combat COVID-19. The study looked at both the humoral and cellular response of the vaccine compared to the natural infection in COVID-19 patients. Additionally, neutralization capacity of a pseudotyped and wild-type SARS-CoV-2 virus was assessed.

Summary of Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

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. 

University of Michigan - Ann Arbor

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

McKay, P.F., Hu, K., Blakney, A.K. et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat Commun 11, 3523 (2020). https://doi.org/10.1038/s41467-020-17409-9

Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice

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

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


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