Strategies of developing specific SARS-CoV-2 vaccine:
Some mRNA vaccines have been developed for SARS-CoV-2 (table 1.), they encode stable form of S protein before its fusion to the host cell membrane and depend mainly on a recent genetic technique which does not involve viral culture in the laboratory but in the human body instead. This method involves mRNA fragments that encode the viral proteins which are then injected into the body, subsequently, the viral proteins are presented by the antigen presenting cells to be recognized by T and B lymphocytes to start the activation of the host antiviral immune response(7). Currently, there are many candidate mRNA vaccines that have been approved by WHO. Most of them are still in the pre-clinical stage of study except an LNP-encapsulated mRNA vaccine developed by Moderna company and is currently in the clinical evaluation stage, phase I (100).
DNA vaccines reflect the new evolutionary path of vaccine production. Genetic manipulation is used to generate the vaccinations produced through recombinant DNA processing. Basically, the DNA which encodes the target protein is inserted into the appropriate cell line or microorganism by a plasmid or viral vector where the DNA is then converted to a protein. Afterwards, the product is extracted by purification technique(101). One of the advantages of DNA vaccines is that it is easy to manufacture such plasmids in big amounts in addition to the long-life immunity they could provide (102).
AZD1222 is a recent DNA vaccine under trial (formerly known as ChAdOx1 nCoV-19) that is using adenovirus vector and targeting SARS-COV-2 S protein resulting in generation of humoral immune response with production of immunoglobulins against the virus. Five hundred and 10 volunteers aged between 18 and 55 years old were enrolled in this single-blind randomized clinical trial study which generated an acceptable safety profile and promising immunogenicity (103).
Preclinical investigations have been done in animal models to test the results and efficacy of another DNA vaccine and has shown good primary outcomes, then it was proceeded to enter human clinical trial, phase I. The vaccine with the name INO-4800 vaccine is involving 40 healthy individuals who are receiving, each, 2 doses of the vaccine with 4 weeks interval in between, then their antibody responses are assessed(104). Other many candidate DNA vaccine are approved by WHO but they are still in the preclinical phase of study.
Similarly, eleven SARS-CoV-2 protein subunit candidate vaccines are approved by WHO, all of them are in the preclinical phase. Examples include capsid-like particle AdaptVac, Drosophila S2 insect cell expression system VLPs and peptide antigens formulated in lipid nanoparticle formulation (100). Protein Subunit vaccines include some epitopes of the virus usually produced through recombinant DNA techniques or viral culture(105). One advantage of this type of vaccines is the relatively fewer number of antigens, hence lower chance of potential side effects. However, this low number of antigenic epitopes could elicit weaker immune response but this disadvantage is treated by conjugating such epitopes with adjuvant proteins to bypass this weakness(106).
Additionally, many replicating and non-replicating viral vector candidate vaccine are being tested for efficacy and safety. Replicating viral vectors such as measles, influenza vector expressing RBD and horsepox vector expressing S protein are in the preclinical experiments phase while non replicating viral vectors such as adenovirus type 5 vector is proceeding to clinical trial phase I and II with favorable initial results in the preclinical phase (100).
Another advanced strategy is the production of vaccines that are formed of virus like particles (VLPs) such as parts of the viral surface proteins. This is a complex procedure that involves processing these particles into more immunogenic proteins that could initiate the host antibody and cell mediated immunity(107). VLP vaccine expressing viral RBD as well as plant derived VLP are being tested pre-clinically and approved by WHO(100).
Inactivated viruses’ vaccines work through including the whole virus which has been deactivated either chemically or physically. These vaccines are more stable compared to other types of vaccines as they are usually maintained in powder form, but unfortunately less effective and more expensive due to its complicated production machinery(108). Three inactivated virus candidate vaccines are in the clinical human trial stage phase III and are approved by WHO(100).
Table 1. Summary of SARS-CoV-2 candidate vaccines proceeding to phase 3 of human clinical trials approved by WHO, August 13, 2020(109)