COVID-19: Everything you need to know about the different vaccines and innovative therapies!

How do vaccines work?

Vaccines protect us by "training" the body to recognize an infectious agent. In fact, in the adaptive immune system there are B lymphocytes that form "memory cells". These memory cells are responsible for "remembering" the pathogens encountered and thus respond more quickly and effectively when they infect the body again. 

The idea is simple: inoculate the patient with a weakened or inactive form of the pathogen (without danger, it is an "empty shell of the pathogen") in order to provoke an immune reaction. Memory cells are then created. The vaccine therefore makes the patient immune to the pathogen. An excellent example of this process is polio, which was eradicated in many countries thanks to vaccination towards the end of the 20th century.

According to the World Health Organization, vaccination prevents 4-5 million deaths each year worldwide and is one of the most cost-effective investments in health.

There are two types of vaccines: preventive and therapeutic. The first type is based on the principles described above, while the second type unlocks the immune system blocked by the pathogen's mechanisms (which has shown promising results in oncology). 

mRNA, viral vector... What are the different types of COVID-19 vaccine?

There are different vaccine strategies: mRNA vaccines, viral vector vaccines and inactive virus vaccines

mRNA vaccines: Pfizer and Moderna

mRNA vaccines are the vaccines marketed by Pfizer and Moderna.

Messenger RNA (referred to as mRNA), is a single-stranded molecule present in all of the body's cells. It is made in the cell nucleus and holds the instructions for making proteins from our genes, in the cytoplasm of the cell.

MRNA vaccines work as follows: An mRNA vaccine is injected into a person's arm, delivering the instructions for making the S protein. Then, the immune system responds, triggering the cells to produce the protein on their surface, which induces immunity against the pathogen (which in this case is COVID-19).

Source: CDC

The Pfizer and Moderna vaccines are 95% and 94% effective against COVID-19, respectively. They must be stored at -20° C (-4° F) for Moderna and -70° C (-94° F) for Pfizer. In addition, two doses are required, 21 days (3 weeks) apart for Pfizer or 28 days (1 months) for Moderna

Viral vector vaccines: Johnson & Johnson, AstraZeneca, Sputnik V

Viral vector vaccines (Johnson & Johnson, AstraZeneca, Sputnik V) use a non-pathogenic virus such as an adenovirus to carry genetic material into the cell. Once in the cell, the transmitted DNA is translated into an S protein, triggering an immune response. In this type of vaccine, there is no penetration of the DNA into the cell genome and no replication of the adenovirus.

Source: CDC

These vaccines have the advantage of being less expensive and of being able to be stored between 2 and 8° C (35.6-46.4° F), but they are less effective: 66.3% for Johnson & Johnson, 82% for AstraZeneca, and 91% for Sputnik V. The Johnson & Johnson vaccine only requires one dose, while AstraZeneca requires two doses spaced 12 weeks apart, and Sputnik V spaced at 21 days apart.

The British-Swedish AstraZeneca vaccine, Moderna and Pfizer-BioNTech vaccines are all authorized and available for use in the UK. In May 2021, the Johnson & Johnson single dose vaccine has been authorized in the UK. The Russian Sputnik V vaccine is not available.

Nanoparticle vaccines: Novavax

The Novavax vaccine, uses nanoparticles coated with protein S, which triggers the immune response. It is 96% effective with 2 doses 21 days apart. Moreover, it can be stored for 6 months at 2 to 8° C (35.6-46.4° F). This vaccine is estimated to be authorized and become available in the UK imminently. 

Inactivated vaccines: Sinovac, Sinopharm, Bharat Biotech

Finally, inactivated vaccines: Sinovac (50% efficacy), Sinopharm (79% efficacy), Bharat Biotech (81% efficacy), use a chemically inactivated virus that can no longer replicate itself. Even when inactivated, the virus still has the S protein on its surface, which triggers the immune response. These three vaccines can be stored between 2 and 8° C (35.6-46.4° F). However, they require 2 doses at 21 (Sinopharm and Bharat Biotech) and 14 days (Sinovac) intervals. None of these three vaccines is currently available in the US, although negotiations are underway for the Bharat Biotech vaccine with a development partner, Ocugen.

Who is eligible for which vaccine?

Source: CDC

The CDC currently recommends that anyone aged 12 and older be vaccinated against COVID-19. As of now, the only vaccine authorized for children and teens aged between 12 and 18 is the Pfizer-BioNTech vaccine.

Reaction responses to the vaccine

The reaction responses reported for the COVID-19 vaccines tend to be common among the 3 vaccines currently available in the UK, namely:

• Headache
• Fatigue
• Localized pain (at the injection site)
• Muscle or joint pain
• Flu-like symptoms (fever, chills, etc.)

Cases of facial paralysis (Bell's palsy) have also been reported, the incidence rate of which is around 7 per 73,000 people. This rate is, however, lower than the overall rate in the general population, which is about 35 per 100,000 people.

Finally, in April 2021, six cases of severe blood clots, cerebral venous sinus thrombosis, in combination with low levels of blood platelets (thrombocytopenia) were reported in women aged between 18 and 48 who had received the Johnson & Johnson vaccine. The CDC and FDA placed the vaccine on pause pending further investigation. After two weeks of analysis and examination, the pause was lifted, as the agencies were unable to find a causal link between the vaccine and the blood clots, though the possibility is not excluded. If these cases were to be correlated to the vaccine, the risk of thrombosis would be 0.00009% (less than 1 in 1 million). It is important to note that when taking a contraceptive pill, the risk of thrombosis is between 0.03-0.09% (between 3 and 9 women in every 10,000 women on birth control pills), the risk is therefore 1,000 times higher with the pill than with the vaccine.

Innovative therapies: Are there any medications to fight COVID-19? 

Vaccines are not the only means being studied to fight COVID-19. 

First, there is the phase 2 study of APN 01 by the Innovative Medicines Initiative (IMI) in Europe. This product, developed by the IMI's MAD-CoV-2 project, is an inhibitor of the ACE2 receptor. Its inhibition would prevent the virus from entering the cells. 

Cathepsin inhibitors are also being studied. Their inhibition would block the release of viral RNA into the cell.

The polyclonal antibody XAV-19, developed by Xenothera, a French biotech company, could limit the virus' damage to the lungs. The polyclonal nature of the antibody allows it to be effective against the different variants in circulation. In addition, the treatment, which is currently undergoing clinical trials in around 20 French university hospitals, was awarded the "national research priority" label in December 2020.

Stemlnov, a biotech company also based in France, is developing a treatment using mesenchymal stem cells (cells that can produce a large number of different cell types). They are thought to have immunomodulatory and anti-inflammatory properties which aid the preservation of respiratory tissues (whose damage comes from the deregulation of the immune response). This therapy was tested by the University of Miami on 24 patients in acute respiratory distress. One month later, a survival rate of 91% (versus 42% with the placebo) was observed.

Finally, a collaboration between the French Curie Institute and the Pasteur Institute is developing a treatment based on extracellular vesicles (a kind of empty cell) that express the ACE2 receptor on their surface. 

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