- 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


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. 

Self-amplifying RNA vaccine

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):

Smith College

Carnegie Mellon University

Wayne State University

- Development of COVID-19 Vaccines
- Types of Vaccines:
     - Virus Vaccines
     - Nucleic Acid Vaccines
     - Viral Vector Vaccines
     - Subunit Vaccines

Genetic Engineering in Vaccine Development 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

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 for COVID-19

Viral-Vector vaccines genetically engineer another virus, referred to as vectors, to carry genetic materials from the coronavirus and produce coronavirus proteins in the human body. These vectors are weakened and does not cause disease. Two main types are (shown in image):

Viral-Vector Vaccines for COVID-19

Virus vaccines use the virus itself, or  in a weakened or inactive form.

Virus Vaccines for COVID-19

Recent efforts to find a possible working vaccine for COVID-19 has allowed vaccine development to be distinct from traditional vaccines. Traditional vaccines for most viruses are either virus-based or protein-based. The idea behind next-generation vaccine platforms is to be able to develop a vaccine based on only sequence information and not by culturing the virus. Some of the non-traditional vaccines currently being developed are viral vector, nucleic acid-based vaccines and antigen-presenting cells.

New methods for COVID -19 vaccine development

Includes the scientific challenges and direction the development of COVID-19 vaccines.
- Challenges of development
- Vaccine antigen selection and design 
- Protective immunity 
- Preclinical evaluation of safety
- Manufacturing 
- Vaccine design itself is complicated
- Need for cold chain
- Consideration of cost
- Global distribution
-Authorization by US Food and Drug Administration and VRBAC
- Goals of development

Development of COVID-19 Vaccines

Nanotechnology is used to create modern vaccines because nanomaterials are best for antigen delivery. Nanotechnology advances have helped novel vaccine candidates to clinical trials at a surprising speed. Nanotechnology and viruses work at the same length scale, which specifically helps vaccine development. mRNA vaccine being developed is delivered through lipid nanoparticles.

Nanotechnology in vaccine delivery

Subunit vaccines use only the essential antigen or other purified protein subunits of the pathogen via a harmless vector that can best stimulate the immune system. The chance of developing an adverse reaction is significantly lower than in other vaccine types and they elicit a strong immune response. However, they often require adjuvants to stimulate an adequate response and it is difficult to identify the precise antigens that induce long-term immunity.

Subunit Vaccine

- NVX-CoV2373 from Novavax Inc
- Anhui Zhifei Longcom / Chinese Academy Vaccine
- CoVLP from Medicago
- rAd26-S and rAd5-S (Sputnik V) from the Gamaleya Center 
- Ad26.COV2.S from Johnson & Johnson
- Ad5-nCoV from CanSino Biologics
- ChAdOx1 nCoV-19 from The University of Oxford
- mRNA-1273 from ModernaTX
- BNT162b2 from Pfizer and BioNTech
- Bacillus Calmette-Guerin (BCG) Vaccine from Murdoch Institute in Australia
- Vaccine from Wuhan Institute of Biological Products Vaccine
- CoronaVac from Sinovac Biotech Ltd
- BBIBP-CorV from Beijing Institute of Biological Products
- BBV152 from Covaxin



Vaccine Candidates of Interest (Lit Review)

• DNA vaccine consists of delivering genes or fragments of it, encoding immunogenic antigens to the host's cells by using DNA plasmids as a vector.

• Compared with traditional live or attenuated vaccines, DNA vaccines have several advantages, such as induction of broad immune responses without any risk being associated with replicating microorganisms; stimulation of both cellular and humoral immunity; construction of a vector encoding different antigens in a single vaccine; efficient large-scale, low-cost, production; and high storage stability

• A clinical trial was designed to evaluate the safety and tolerability of orally immunized bacTRL-Spike vaccine in healthy adults. However, this study has not yet started recruiting, and the estimated completion date is December 31, 2021 Moreover, the safety and immunogenicity of GX-19, another DNA vaccine against COVID-19 that uses intramuscular immunizations are already in clinical trials.

• mRNA vaccines do not need to reach the cell nucleus like the DNA ones, which is one of the potential practical advantages. The mRNA-1273 (Moderna Inc. Cambridge, MA, USA) was the first mRNA vaccine to be designed against COVID-19 and has achieved a time record of 63 days from vaccine design to human trials.

• Developing vaccines against COVID-19 require further studies on gene mutations and how to avoid vaccine failure because of them.

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