Steps in the development of the Valneva vaccine

The Franco-Austrian laboratory Valneva has developed VLA2001, currently the only inactivated virus vaccine against Covid-19. London, which had ordered 100 million doses, has just terminated its contract. What is its principle? Its efficiency ? Where are the clinical trials at? When in France? Questions answers.

[Mis à jour le mercredi 15 septembre à 11h42] The Franco-Austrian laboratory Valneva has developed the only inactivated virus vaccine against Covid-19 in clinical development in Europe. However, the company announced in a statement of Monday, September 13, 2021 to have received “a termination notice” from the British government, about the “supply agreement” of its vaccine VLA2001. As a result, the laboratory’s stock price fell by 40%. As a reminder, the British government had ordered 100 million doses for 2021-2022 for a contract amounting to 1.4 billion euros. The laboratory indicates that the government “claims that Valneva failed in his obligations, which Valneva vigorously contests “. However, the European Union remains interested in the anti-Covid 19 vaccine from the Valneva laboratory and is continuing its negotiations, the French government assured on September 14. The society “continues to be fully engaged in development” of its vaccine and “will increase its efforts with other potential customers to ensure that its inactivated vaccine can be used in the fight against the pandemic”. Phase 3 clinical trials are still ongoing and results are expected early in the 4th trimester. These results “will be part of the progressive submission of the VLA2001 conditional authorization application dossier to the UK health agency. Subject to Phase III results and UK Health Agency approval“. The director general hopes for an effectiveness against the Covid-19 of at least”80%“. If this is the case, Valneva’s vaccine may benefit from a marketing authorization (MA), potentially before the end of 2021. What is its principle ? What are the results of clinical trials? When can it see the light of day in France? Knowledge to date.

The vaccine developed by the Franco-Austrian laboratory Valneva is called VLA2001.

Valneva is a Franco-Austrian laboratory based in Saint-Herblain, in the suburb of Nantes. A few months after the start of the pandemic, it announced the development of its inactivated virus vaccine. “When we launched in April 2020, we did not have the funding, we started, with our own resources, to test our mouse models. Especially since at the beginning nobody knew how the infection was happening. We had extremely strict measures in the laboratory to ensure that people were really very, very well protected “, says Franck Grimaud, its president. Valneva has already signed a contract with the United Kingdom for delivery before the end of 2021 if the clinical trials are positive.

Steps in the development of the Valneva vaccine © Valneva

Whole inactivated vaccines are usually less efficient than live attenuated vaccines.

VLA2001, currently the only candidate inactivated virus vaccine against Covid-19 in clinical development in Europe. In other words, it is a vaccine made up of killed viruses. According to an article published on the website of the World Health Organization, it is possible to manufacture a vaccine “taking the virus or bacteria that carry the disease, or a very similar one, and to inactivate or kill it with chemicals, heat or radiation“. As the virus is killed, so it is totally unable to multiply and therefore cause disease. How? ‘Or’ What ? By activating the specialized white blood cells of the immune system (B lymphocytes and T lymphocytes) which will release antibodies into the blood capable of binding to the virus targeted by the vaccine. Thus, some of these antibodies neutralize the microbe to prevent it from entering human cells. Others eliminate viruses, so that they cannot cause disease or complications. This inactivated virus vaccine method uses technology that has been proven in humans. “This is a traditional vaccine technology, used for 60 to 70 years, whose methods are proven and which enjoys a high level of security. Most influenza vaccines and many childhood vaccines use this technology“, states the European Commission in a statement of January 12, 2021. However, whole inactivated vaccines are generally less efficient live attenuated vaccines and often require multiple doses or boosters, says the Swiss InfoVac site. This is therefore a different principle from attenuated virus vaccines. A live attenuated vaccine uses a live but weakened version of the virus or a very similar version.

Differences between an inactivated virus vaccine and an attenuated virus vaccine

Vaccines Inactivated virus vaccines Attenuated virus vaccines
Composition Virus killed Live but weakened viruses or a very similar version
Advantages

– Cause very few side effects

– Can be given to people with weakened immune systems.

– Can be manufactured on a large scale

– More effective than attenuated virus vaccines

Disadvantages

– Requires special laboratory facilities to safely grow virus or bacteria

– Manufactured to a reasonable scale

– Can have a relatively long production time

– Requires administration in two or three doses.

– Less effective than attenuated virus vaccines

– Not suitable for people with weakened immune systems.
Examples

– Vaccines against influenza and polio

– Chinese vaccines Sinovac and Sinopharm, Franco-Austrian vaccine Valneva

– ROR Vaccines,

– Vaccines against chickenpox and shingles

Clinical trials of phase III are still in progress. “On the basis (…) of the phase I and II trials, it is hoped have a vaccine that is more than 80% effective. It will have to be demonstrated in the phase III trial“, indicated Franck Grimaud, the director of the laboratory on BFM Business. Its efficacy would therefore be lower than vaccines with Messenger RNA, like those developed by Pfizer-BioNTech or Moderna (efficiency around 95%) but superior to vaccines viral vector like those of AstraZeneca or Johnson & Johnson (efficiency around 60-70%).

The VLA2001 vaccine was well tolerated and no safety issues have been identified.

Valneva posted results of phases I and II of its clinics in early April 2021. The VLA2001 vaccine was well tolerated and no safety issues have been identified. In the group vaccinated with the highest dose of the vaccine, the seroconversion rate of immunoglobulin G was 100% and the titers of neutralizing antibodies at the same or higher level than those generally seen in sera from convalescent persons. Based on these results, Valneva decided to use the highest dose of its vaccine in the Phase III clinical trial, serving to prove the true effectiveness of a vaccine before it is potentially released to the market. The first part of this clinical trial is currently taking place in the United Kingdom, with adult patients of all ages. More than 4000 participants in the UK were randomized to the pivotal phase III “Cov-Compare” study which compares the efficacy of the vaccine from Valneva to that of the vaccine from AstraZeneca (Vaxzevria). The first results are expected at the start of the fourth quarter of 2021. These results “will be part of the progressive submission of the VLA2001 conditional authorization application dossier to the UK health agency. Subject to Phase III results and UK Health Agency approval“. In addition, at the beginning of August, Valneva launched an additional trial in New Zealand, with people over 56 years old, the age group most at risk for Covid-19.

The Valneva vaccine will be administered intramuscularly.

In clinical trials, Valneva vaccine has been administered in two doses for the majority of participants:

  • The first at JO
  • The second on D21, i.e. three weeks after the first dose

As part of the VLA2001-201 study (phase 1/2), tkings doses of VLA2001 vaccine (low, medium, high), given twice three weeks apart in 153 young adults healthy people aged 18 to 55, were tested.

In phases 1 and 2 of the clinical trials, VLA2001 was generally well tolerated in all groups tested (three dose levels), with no safety concerns identified by an independent safety data monitoring committee. , reports the laboratory. The majority of adverse events (AEs) were mild or moderate and only two subjects reported serious solicited side effects: headaches and fatigue. All of the requested side effects were transient. Only 17.6% of unsolicited effects up to day 36 were considered vaccine-related and no serious vaccine-related effects were reported.

At the moment, Valneva’s vaccine is in clinical trials. If at the end of these clinical trials, the efficacy is validated, it may be marketed. The laboratory is currently focusing on the European market. In January 2021, Valneva announced that it was in advanced discussions with the European Commission (EC) for the supply of up to 60 million VLA2001. In July 2021, the company reported that these discussions were still ongoing. In September 2020, Valneva announced a collaboration with the British government which has an option to buy up to 190 million doses vaccine until 2025. To date, the UK government has ordered 100 million doses available in 2021 and 2022 and retains options to order 90 million additional doses between 2023 and 2025, we can read on the site of Valneva.

Sources :

– Site de Valneva : Valneva Reports Positive Phase 1/2 Data for Its Inactivated, Adjuvanted COVID-19 Vaccine Candidate, VLA2001

– The different types of vaccines against Covid-19, WHO, January 12, 2021

– European Commission press release, January 12, 2021.

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