The international Phase III study of the Sanofi vaccine aims to evaluate the safety, efficacy, and immunogenicity of a vaccine candidate: it began on May 27, 2021, for the Sanofi recombinant protein vaccine. It could therefore be approved in the fourth quarter of 2021, subject to convincing results from this phase III as well as regulatory evaluations.
This vaccine may be useful, in particular as a possible booster after two doses of mRNA vaccine, but also to participate in the vaccination campaign of the world population, a little less than a quarter of whom are, to date, vaccinated.
Context of Covid-19 vaccination
The Covid-19 pandemic is an unprecedented global health crisis.
A French transnational company whose activities include pharmaceuticals and vaccines, Sanofi ranks third in the world in the healthcare sector by turnover. Its global Vaccines entity is based in Lyon and is called Sanofi Pasteur. She is currently working on two Covid-19 vaccine candidates that use two different technologies. It is, on the one hand, an adjuvanted vaccine based on recombinant proteins, and, on the other hand, a messenger RNA vaccine (the same technology as the Pfizer and Moderna vaccines).
What is the principle of the Sanofi vaccine?
According to Our World in Data, only 24.6% of the world's population is currently fully vaccinated. In addition, large disparities remain in terms of immunization between, on the one hand, the richest countries and, on the other, the countries with lower incomes.
In this context, the arrival of a new vaccine, in this case, the very first French vaccine with Sanofi, is scheduled for the end of the fourth quarter of 2021, subject to the results of the phase III clinical trial.
This vaccine called Vidprevtyn could help boost the vaccination campaign around the world. Especially since recombinant proteins, the technology used by this vaccine candidate, is easier to preserve than other vaccines such as those based on mRNA technology.
Operation and principle of action
Sanofi and GlaxoSmithKline (or GSK, a British pharmaceutical company), have launched since May 27, 2021, the third phase of clinical trials of their recombinant protein vaccine candidate against Covid-19.
It is a protein-based vaccine: it contains a version of the Spike protein grown in the laboratory. This vaccine under development is based on the same technology used for one of Sanofi's seasonal influenza vaccines, with the flu protein being replaced by the Spike protein. This protein is present on the surface of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2, which is the coronavirus at the origin of Covid-19), it allows the coronavirus to enter human cells, including those of the lungs. Once entered a cell thanks to Spike, the virus reproduces, before spreading to other cells in the body.
In fact, this recombinant protein vaccine candidate from Sanofi is based on innovative technology. Its purpose is to induce an immune response that will allow the human body to fight against the Covid-19 virus. GSK produces adjuvants for pandemic use.
When a person receives the vaccine, their body identifies the Spike protein as foreign and makes antibodies against it. If later, the vaccinated person comes into contact with SARS-CoV-2, the immune system will recognize the viral protein and be ready to defend the body against the virus.
The principle of this proven technology is as follows:
- To make the vaccine, scientists copy the DNA sequence of the Spike protein in the lab.
- Then, they introduce this DNA sequence into a circular fragment of DNA called a plasmid: it is, therefore, a recombinant DNA since it recombinants several DNA fragments.
- This plasmid carries the DNA sequence of the Spike protein into a baculovirus, which is a kind of delivery system used for the manufacture of the vaccine.
- In parallel, scientists are developing cells in culture: these will serve as a production platform. Baculovirus can then enter these cells and reproduce there.
- This results in the production of multiple identical copies of the Spike protein.
- The scientists will then extract the Spike proteins, purify them before gathering them in batches, formulating them, and packaging them into vials. This vaccine candidate must be combined with an adjuvant that will boost the immune system so that it defends itself, via the production of antibodies against the Spike protein.
- If the vaccine is injected into the body, the immune system will detect the Spike protein and produce antibodies that can identify and bind to it.
- The immune system reacts to the vaccine. It memorizes the Spike protein. And so, when the body encounters the complete SARS-CoV-2 virus, it will remember that it must generate new antibodies in order to fight the virus. It is this process of memorization that allows a vaccine to provide more long-lasting protection against the disease.
The safety and efficacy of this vaccine is currently still being evaluated by a regulatory authority.
Composition
The vaccine candidate developed by Sanofi-Pasteur and GSK, Vidprevtyn, consists of recombinant Spike proteins produced by Sanofi as well as an adjuvant produced by GSK. One dose of vaccine candidate contains, specifically, an amount of 10μg of recombinant protein, combined with GSK's AS03 adjuvant.
Who can receive the Sanofi vaccine?
Phase III clinical trials of this vaccine are currently underway and involve 35,000 people aged 18 years and older. This is a randomized, double-blind study. Some participants in this study receive the vaccine candidate, others the placebo.
These clinical trials are conducted in different locations around the world: the United States, Asia, Africa and Latin America. This phase III study will therefore make it possible to evaluate, in adult individuals of different ages, to evaluate both the safety and the efficacy and immunogenicity of this vaccine based on recombinant proteins. Depending on the results, the Sanofi vaccine could hit the market for a variety of audiences, potentially starting in the fourth quarter of 2021.
What is the dosage of the Sanofi vaccine?
What is the recommended duration between the 2 injections?
It will also take two doses of the Sanofi vaccine for primary vaccination. For a booster vaccination, one dose will be sufficient. In phase II dose-finding trials, both injections were administered twenty-one days apart. The method of administration is intramuscular.
Should you get vaccinated when you have had Covid?
Phase II clinical trials of the recombinant Sanofi vaccine candidate have demonstrated elevated antibody concentrations observed in participants who have already been infected following the administration of a single dose of this vaccine candidate. They thus suggest that such a vaccine could be useful for vaccination after having already been infected with Covid-19, but also for a booster vaccination.
How is the Sanofi vaccine stored?
Proteins turn out to be relatively stable molecules. This is why a candidate vaccine designed from purified Spike proteins can be stored at a temperature of 2 to 8°C.
Is the Sanofi vaccine effective?
Protection against covid-19
The percentage efficacy of the Sanofi vaccine will be determined during the ongoing Phase 3 clinical trial. This vaccine candidate has been manufactured to generate a consistently high immune response. In addition, it could potentially stop viral transmission, as reported by the Clinical Trials Arena website.
In fact, the interim phase II results are already known: they indicate that the recombinant adjuvanted vaccine candidate triggered a strong immune response in adults of all age groups. For this, seroconversion rates were between 95% and 100%. In addition, high concentrations of neutralizing antibodies were produced, at levels comparable to those generated by a natural infection.
Protection against variants
The Phase III clinical trial is designed in two stages:
The first step
It aims to determine the efficacy of a vaccine formulation targeting the original Wuhan variant (D.614).
The second step
This one will investigate a different formulation using the South African variant (i.e. The Beta variant, B.1.351).
However, in fact, as evidenced by recent scientific data, the antibodies generated against the South African variant could offer broader cross-protection and therefore protection against other variants that are more transmissible. The design of this clinical trial, therefore, has the objective of also testing the effectiveness of the vaccine against different variants in circulation.
1 dose: limited efficacy?
To be effective, the vast majority of vaccines require boosters, because otherwise, their effectiveness is not optimal. And so, for Sanofi's vaccine, it is the injection of two doses that are currently being tested for primary vaccination.
A single dose could be useful either as a booster after vaccination with another vaccine, for example, an mRNA vaccine, or in people who have previously been infected with Covid-19.
What are the side effects of the Sanofi vaccine?
In a statement, Sanofi announced that with respect to adverse reactions to this recombinant protein vaccine candidate, "the safety profile is acceptable and does not raise safety concerns."
The results of phase III clinical trials will make it possible to better determine, in particular, the safety of this vaccine and the nature of its side effects.
What are the differences with other vaccines on the market?
Sanofi vs Pfizer or Moderna
The technology of these vaccines is different, since Sanofi uses that of recombinant proteins, while the Pfizer vaccine, like Moderna's, uses messenger RNA technology.
Thus, the difference between these two types of vaccines is that, in the case of Sanofi, the vaccinated person is injected directly with a Spike protein produced by biotechnology, combined with an adjuvant that stimulates the immune response, while in the case of Pfizer (or Moderna), it is the messenger RNA encoding the Spike protein that is injected, thus causing the body's cell itself to produce the Spike protein that will trigger the immune response. An important difference is also that the Sanofi vaccine requires the addition of an adjuvant, whereas messenger RNA technology does not.
Sanofi vs Astrazeneca and Janssen
Again, the two technologies diverge between Sanofi's vaccine candidate and the Astrazeneca or Janssen vaccines. For this, the technology of the AstraZeneca vaccine and that of the Janssen vaccine uses an adenoviral vector.
The Spike protein is not injected directly in combination with an adjuvant, as with Sanofi's Vidprevtyn vaccine, but this Spike protein, in the case of AstraZeneca or Janssen vaccines, is expressed by means of an adenovirus, which is a recombinant chimpanzee virus. It should also be noted that the Sanofi and AstraZeneca vaccines require, for primary vaccination, two doses of vaccines while that of Janssen requires only one.
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