Vaccines against covid-19: how they work and in what phase each project is

There are currently about 200 vaccine candidates in clinical trials , in clinical phases 1 to 3. The objectives of vaccines in clinical trials are three:

1. Show that they are safe.
2. Prove that they activate the immune system in humans.
3. Check its effectiveness, that is, its ability to protect against the SARS-CoV-2 virus.

Protection efficiency can be achieved by prevention of infection, transmission and severity of symptoms.

A vast majority of vaccines in development tend to focus on preventing infection and target protein S, which is the site of contact with cells, with the intention of developing neutralizing antibodies.

However, the site of contact of protein S with the cell, the RBD region, is hidden in its structure, so to achieve neutralizing antibodies, vaccines should focus on other parts of that protein or even look at other antigens as well. of the virus.

Most vaccines have managed to pass the first phase, that of toxicity and safety. Therefore, a fairly high number of possible vaccines are in phase 2. In this phase they have already proven their immunogenicity, that is, that the vaccination succeeds in inducing an adequate response of antibodies that recognize the virus and cytotoxic T cells, which they are the ones that fight the virus effectively.

But the great challenge is for them to be able to demonstrate that they can protect against covid-19. In this kind of urgency that the pandemic has demanded from pharmaceutical companies and academic institutions, very innovative designs are being used and alliances and collaborations that had not been carried out until now are being made. The objective was to obtain adequate funds to achieve its development on a global scale.

More advanced vaccines

The vaccines that are in the first line, or in phase 3, currently number 9 and use five different types of formulations:

• Inactivated vaccines , that is, whole SARS-CoV-2 viruses that have been inactivated and cannot multiply. This approach is the most conservative since the current viral vaccines in our vaccination schedule are the majority of this type.

• Protein or peptide vaccines called subunits . Instead of using the entire virus, these use only the proteins or smaller parts, such as peptides, that can be obtained through recombinant biotechnology in the laboratory. These vaccines are very safe and cheap to produce, but have the disadvantage of requiring adjuvants or amplifiers of the immune response. In addition, they require several doses to stimulate an adequate immune response against SARS-CoV-2.

• Vectors with non-replicative or replicative viruses . That is, non-replicative viruses that are genetically modified to reduce their virulence and make them non-replicative. The most common are adenoviruses in humans or in other species such as chimpanzees or poxviruses, which include the S protein of covid-19. This protein that binds to the specific receptor ACE2, the enzyme 2 that converts angiotensin and is its route of entry. Their disadvantage is that there may be insufficient immunity, since being complete viruses they are highly immunogenic. The attenuated replicative viruses are viruses of other types, such as measles, polio or smallpox, but attenuated and modified to produce the S protein of SARS-CoV-2. These vaccine designs present the possibility that viruses can reverse their virulence in some cases.

• Nucleic acid vaccines, that is, they are the genetic material of the virus, either RNA or DNA. Messenger RNA viruses are those that are in more advanced stages. The RNA is usually the one that codes, that is, it will produce a single target antigen, usually the protein S. To protect them from being degraded, they are normally encapsulated in nanoparticles composed of lipids. They have the advantage of their safety and immunogenicity, but also some drawbacks, such as the need to be stored at very low temperatures (less than 0ºC), which makes it difficult to export them to all countries. On the other hand, DNA vaccines tend to be poorly immunogenic, they have to be expressed in antigen presenting cells or APCs, and to increase their immunogenicity they are usually put in nanocarriers such as viral-like particles or VLPs.

• Nanoparticle-based vaccines . These latest vaccines have high potential for their safety, their immunogenicity, and their ability to target antigen-presenting cells. They also have the capabilities of adjuvants, that is, of amplifiers of the immune response.

Other types of vaccines in clinical trials

There are also other types of vaccines that are in less advanced stages, in phase 1 or 2, but with good development possibilities. Among them we find:

• DNA vaccines , with plasmids to produce protein S with a new vaccination system without needles such as that of Inovio Pharmaceuticals, or DNA plasmids with protein S and an adjuvant that amplifies the immune response, such as the one from the University of Osaka-Anges- Takara Bio in Japan.

• Recombinant proteins such as GSK-Sanofi-Dynavax from the US, UK and China with an adjuvant or amplifier of the immune response developed by the pharmaceutical company GSK; that of Vaxine Ptd.-Meditox in Australia which contains a protein S and an adjuvant developed by the group and which is called Advax; or that of the University of Queensland in Australia, which also consists of a protein S molecular clamp together with the adjuvant MF59.

• Replicative viruses with a measles virus vector, TMV-083 led by the Pasteur Institute in France.

• Repurposed vaccines, vaccines directed at other pathogens such as the bacterium Mycobacterium bovis, BCG, which also protect against coronaviruses in a non-specific way, which has also been suggested for the oral polio and measles vaccines.

Full release forecast of results

The pressure exerted from governments, society and global health organizations is so high that many of the companies have eliminated phases by increasing the number of volunteers recruited.

These total 10,000 Novavax volunteers, 30,000 Moderna volunteers, 44,000 Pfizer volunteers, 50,000 Astrazeneca volunteers, or 60,000 Jansen volunteers. However, there is not much information on the number of volunteers in Chinese or Russian companies.

According to forecasts, the first vaccines that will release their results will be Moderna and Pfizer in December 2020 and Astrazeneca in January 2021.

Carmen Álvarez Domínguez, Biochemist and molecular biologist, professor of Health Processes at the Faculty of Education and researcher in Immunotherapy, UNIR – International University of La Rioja

This article was originally published on The Conversation. Read the original.