December 4, 2020

how they work and in what phase is each project

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. Prove 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.

The 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 they 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. of the virus.

Most vaccines have passed 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 is able to induce 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 big challenge is for them to be able to show 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 vaccinesi.e. complete 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 vaccines or peptides called subunits. Instead of using the whole virus, these use only the proteins or smaller parts, such as peptides, that can be obtained by recombinant biotechnology in the laboratory. These vaccines are very safe and cheap to produce, but they 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 ACE2 receptor, the enzyme 2 that converts angiotensin and is its route of entry. Its disadvantage is that insufficient immunity may exist, since being complete viruses they are very immunogenic. Attenuated replicative viruses are viruses of other types, such as measles, polio, or smallpox, but are 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 S protein. 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 into nanocarriers such as viral-like particles or VLPs.
  • Nanoparticle-based vaccines. These latest vaccines have a high potential for its safety, its immunogenicity and its ability to target antigen-presenting cells. They also have capacities as adjuvants, that is, as amplifiers of the immune response.

The following table lists the nine most advanced phase 3 vaccines, the type of formulation and the vectors they carry. It also includes the company that develops them, the country, the number of doses needed, their form of immunization, and the results of the reported trials.

Characteristics of the 9 vaccines in phase 3

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 needleless vaccination system such as that of Inovio Pharmaceuticals, or plasmids DNA with protein S and an adjuvant that amplifies the immune response, such as that of the Osaka-Anges-Takara Bio University in Japan.
  • Recombinant proteins like that of the GSK-Sanofi-Dynavax from USA, United Kingdom 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, it is also composed of a protein S molecular clamp together with the adjuvant MF59.
  • Replicative viruses with a vector of the measles virus, TMV-083 led by the Pasteur Institute in France.
  • Reused vaccines, vaccines directed at other pathogens such as that of 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 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 add up to 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.

The Conversation

East Article was originally published in The Conversation. You can read it here.


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