Approved Vaccines Against COVID-19

Since the beginning of the COVID-19 pandemic, focus has been split between treatment and vaccination. Many drug therapies used in the attempt to treat COVID-19 failed to show significant efficacy, while at the same time numerous vaccine trials were underway. The wearing of masks, sanitisation of hands, and expectation to social distance successfully curbed the transmission of the virus and eliminated it from certain countries, however in other countries the infection rate is again on the rise. At the end of 2020, we are now seeing the end of many of these fast-tracked vaccine trials and the beginning of a widespread vaccine distribution effort.

There are currently 5 approved vaccines (Figure 1) currently being selectively distributed around the world and a further 5 vaccines in phase 3 of vaccine trials (Figure 2).

Figure 1: Currently Approved Vaccines

Figure 2: Phase 3 Trial Vaccines

There are many methods to create a vaccine as indicated by the types of vaccines in the above two figures. It is vital to understand the difference between these forms of vaccines as their side effects, storage and distribution, number of booster shots, and their efficacy may differ.

The first type of vaccine that will be discussed is the mRNA-based vaccine. The first successful mRNA-based in vitro vaccine trial was performed in mice in 1990. This was the first time that a detectable level of protein was made in response to an administered mRNA. Another trial done in 1992 using vasopressin-encoding mRNA also elicited a physiological response in rats and therefore the results of mRNA use for vaccinations looked promising. There was, unfortunately, no further development into this field after 1992 due to concerns over mRNA instability, unwanted and exaggerated immunogenicity, and problems with delivery. There are, however, many benefits to mRNA vaccines. 1) They are able to instruct cells to produce a protein that triggers an immune response in the human body, subsequently leading to antibodies and protection from actual infection. 2) mRNA itself is non-infectious and cannot cause disease itself. 3) mRNA vaccines can be rapidly and inexpensively produced and therefore will be more beneficial to low-income countries. There has never been a licensed mRNA vaccine, although research has gone into mRNA vaccines for influenza, zika, rabies, and cytomegalovirus. This newly approved mRNA vaccine for SARS-COV-2 will be a milestone in the future creation of vaccines.

The second vaccine type that has been approved was developed in China and is an aluminium salt-based adjuvant (alum) inactivated vaccine. This type of vaccine was the first adjuvants used in licensed human vaccines and are still the most widely used due to their vast ability to strengthen immune responses and their high safety profile. An example of the previous use of this type of vaccine is for the H7N9 influenza virus, where it proved safe and strongly immunogenic. In the limited trials done for SARS-COV-2, it appeared to enhance the humoral immune response when the alum was formulated with the S protein or receptor-binding domain. This response was indicated by the increase in IgG titres, high affinity of neutralising antibodies, and production of long-lasting B lymphocytes. The complication with this vaccine is that it seems to be associated with a high Th2 response, causing increased eosinophils and inflammatory cells. This has the potential to cause vaccine-enhanced respiratory disease in individuals predisposed to anaphylaxis and allergy, however no cases of this have to date been reported.

The third vaccine type is the use of a viral vector. The most commonly used viral vectors are the adenovirus, measles virus, and human parainfluenza virus. These vectors are genetically modified so that they are not able to replicate and remain in an attenuated state that is still able to trigger a desired immune response in the human body. The Russian-created vaccine (and one of the phase 3 Chinese vaccines) was made using the adenovirus as a vector. Adenovirus-based vaccines have previously shown the advantage of inducing both an antibody-mediated as well as a T cell-mediated immune response. The problem with this method of vaccination is that in order to achieve an adequate immune response, more than one dose is required. This also leaves the individual unprotected for a longer period as immunity is not immediate.

The last vaccine type that has been approved is the synthetic peptide vaccines. These are chains of 20-30 amino acids that contain a specific epitope of an antigen related to the infectious disease. The advantage to these vaccines is that they are inexpensive to make, they are inherently stable, and have high safety profiles. Unfortunately, no peptide vaccines have been approved by the Food and Drug Association despite over 500 peptides progressing to clinical trials. This is due to the limitation of a single peptide as a vaccine candidate, easy immune evasion, failure to elicit a prolonged and controlled immune response, and lack of clinical efficacy. The difference with the peptide vaccine for SARS-COV-2 is that it utilises a multiepitope-based peptide in comparison to a single-based peptide, therefore triggering a more effective and prolonged immune response.

The above-mentioned vaccines may have been approved for distribution but more time and research is needed to properly assess their efficacy in combating COVID-19.

References:

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