The Franco-Austrian laboratory Valneva has developed the only inactivated virus vaccine against Covid-19. The EMA will begin to examine its application for marketing in Europe, announces the company. Name, date of availability in France, composition, efficacy, side effects… All about VLA2001.
[Mise à jour le 19 mai 2022 à 12h46] the Franco-Austrian laboratory Valneva developed the only inactivated virus vaccine against Covid-19 (VLA2001) in clinical development in Europe. On May 19, the company announces by communicated what’European Medicines Agency (EMA) has accepted the submission of the marketing authorization file of the VLA2001. The vaccine candidate will now be assessed by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Her decision could intervene in next june. The European Commission will review the CHMP recommendation and issue its final decision immediately on the marketing authorization for this new vaccine against Covid-19. Valneva’s vaccine is authorized in the United Arab Emirates since May 16, 2022, at UK since April 2022 and Kingdom of Bahrain since March 2022. What is its principle ? What are the test results clinics? When will it arrive in France ? Is it effective against variants? Omicron? Knowledge to date.
What is the name of Valneva’s vaccine?
The vaccine developed by the Franco-Austrian laboratory Valneva is called VLA2001.
When will Valneva be available in France?
On May 19, 2022, Valneva announced via communicated what’European Medicines Agency (EMA) has accepted the submission of the marketing authorization file of the VLA2001. The vaccine candidate will be evaluated by the EMA’s Committee for Medicinal Products for Human Use (CHMP). Her decision could intervene in next june. The European Commission will review the CHMP recommendation and issue its final decision immediately on the marketing authorization for this new vaccine against Covid-19. On November 24, 2021, Valneva and the European Commission (EC) announced that they have reached an agreement of up to 60 million doses of Covid-19 vaccine by 2023 (24.3 million doses of the vaccine in 2022 and the rest in 2023).
For who ?
In its various press releases, Valneva specifies that the “targeted” indication of its vaccine candidate is a immunization activates populations at risk of Covid aimed at prevent transmission of the virus or a symptomatic infection to Covid-19 as well as “potentially a routine vaccination including against variants“.
How effective is Valneva against Covid?
The Valneva vaccine does not appear to be more effective than the RNA vaccines from Pfizer and Moderna against Covid. Nevertheless, according to Phase 3 trial results conducted on 4012 participants aged 18 and over recruited from 26 sites in the United Kingdom, it is more so than that of AstraZeneca. In the trial, antibody titer levels were higher in subjects vaccinated with Valneva’s candidate compared to those who received AstraZeneca’s vaccine. VLA2001 elicited a broad interferon gamma-producing T cell response specific against S, N and M proteins. And it was “well tolerated, showing a statistically significantly better safety profile than that of the comparator vaccine” the company says in its press release.
How effective is Valneva against the Omicron variant?
The Omicron variant presents 32 mutations (according to the WHO) on its Spike protein, the key allowing SARS-CoV-2 to enter our cells and multiply. The Spike protein is the target of messenger RNA vaccines. But because of its high number of mutations present on its Spike protein (much more than the Delta variant for example), the Omicron variant is more resistant to messenger RNA vaccines (vaccine technology from Pfizer and Moderna). The Valneva vaccine, which is based on another technology (inactivated virus vaccine) may have an advantage over RNA vaccines and be more effective against Omicron. In January 2022, the results of a preliminary study carried out by the Valneva laboratory indicated that the antibodies from serum of 30 people vaccinated with three doses of the VLA2001 vaccine neutralized the Omicron variant. Serum from 30 participants was used in a test to assess the neutralization of the historic SARS-CoV-2 virus as well as that of the Delta and Omicron variants. All 30 samples (100%) showed neutralizing antibodies against the historical virus and the Delta variant, and 26 samples (87%) against the Omicron variant. The average reduction in neutralization compared to historical virus was 2.7 times for Delta and 16.7 times for Omicron.
What is the origin of Valneva’s vaccine?
Valneva is a Franco-Austrian laboratory based in Saint-Herblain, in the suburbs of Nantes in France. A few months after the start of the pandemic, he announced the development of his inactivated virus vaccine. “When we start in April 2020, we don’t have the funding, we started, with our own resources, to experiment with our mouse models. Especially since at the beginning no one knew how the infection was happening. We had extremely strict measures in the laboratory to make sure that people were really, really well protected.” says Franck Grimaud, its president.
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 World Health Organization websiteit is possible to manufacture a vaccine “taking the disease-carrying virus or bacteria, or one very similar to it, and inactivate or kill it with chemicalsheat or radiation“. As the virus is killed, so it is totally unable to multiply and therefore cause disease. How ? By activating the specialized white blood cells of the immune system (B lymphocytes and T lymphocytes) which will release antibodies in 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. “It is a traditional vaccine technology, used for 60 to 70 yearswhose methods are proven and which benefits from a high level of security. Most flu vaccines and many childhood vaccines use this technology“, says the European Commission in a statement of January 12, 2021. However, whole inactivated vaccines are generally less efficient than live attenuated vaccines and often require multiple doses or boosters, says the Swiss InfoVac website. It 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 (such as Valneva) | Attenuated virus vaccines |
|---|---|---|
| Composition | Viruses 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 | – Require special laboratory facilities to safely grow the virus or bacteria – Manufactured to a reasonable scale – Can have a relatively long production time – Require 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 poliomyelitis – Chinese vaccines Sinovac and Sinopharm, Franco-Austrian vaccine Valneva | – MMR vaccines, – Vaccines against varicella and shingles |
What is Valneva made up of?
VLA2001 consists of inactivated particles of the SARS-COV-2 virus having a high density of protein S, conjugated with two adjuvants, alum (aluminum hydroxide) and CpG 1018 (composed of the bases C (cytosine) and G (guanine ) found in DNA). CpG 1018 adjuvant is a component of the HEPLISAV-B vaccine® approved by the American (FDA) and European (EMA) health authorities.
The VLA2001 vaccine could be used as a booster.
How is Valneva administered?
Valneva’s vaccine is administered intramuscularly.
How many doses of Valneva do you need?
In clinical trials, Valneva’s vaccine was 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
Valneva teams are currently conducting trials to study the efficacy of the vaccine as a booster dose. In December 2021she confirmed “an excellent immune response after a third dose of VLA2001 administered seven to eight months after the second dose of the primary series”. More recently, a clinical trial was launched in May 2022 on the people who have either been primed with an RNA vaccine messenger be naturally infected with the COVID-19 virus. The data, if positive, could support a possible use of VLA2001 as a booster vaccine, subject to obtaining regulatory recommendations and clearances. The trial will be conducted in the Netherlands and the first results are expected in the third quarter of 2022.
What are the side effects of Valneva?
In phase 1 and 2 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. In the Phase 3 trial, it “proved to be more favorable, in a statistically significant way, in comparison with the other vaccine used in the trial (that of AstraZeneca (AZD1222), editor’s note)” the company said. A “significantly” lower number of adverse effects monitored seven days after vaccination were found in participants aged 30 years and over, whether in terms of injection site reactions (73.2% for VLA2001 versus 91.1% for AZD1222) or systemic reactions (70.2% VLA2001 versus 91.1% for AZD1222). No unsolicited serious adverse effects were observed. Less than one percent of trial participants reported side effects of particular interest in both vaccine groups. Participants in the younger group vaccinated with VLA2001 showed a safety profile comparable to that of the older group.
Sources:
– The EMA accepts the submission of the marketing authorization dossier for Valneva’s inactivated vaccine candidate against COVID-19. Valneva. May 19, 2022
– Valneva website: 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, 12 January 2021
– European Commission press release, 12 January 2021.