“Bivalent” Covid vaccines targeting the Omicron variant have been administered in France, as a booster dose, since October 2022. In April 2023, the study by French researchers reassured about the cardiac side effects of the Pfizer vaccine.
Vaccination with bivalent vaccines (targeting the Omicron variant) was launched on October 3, 2022 in France, for booster doses. These vaccines have been authorized by the High Authority of Health in September and in November fter being validated by the European Medicines Agency (EMA). These are vaccines manufactured by Pfizer or by Moderna. Their administration is supported by the French health authorities who believe that they are “better adapted to circulating variants, and can contribute to vaccine efficacy against infection“. THE WHO experts estimated at the end of October that “the data is not sufficient to favor them over others booster vaccines”. In January 2023, a alert is given in the United States on a possible increased risk of ischemic stroke after administration of Pfizer’s bivalent vaccine. French researchers from the group Epi-Lighthouse (created by ANSM and CNAM) wanted to assess this risk. Their study published in April 2023 in The New England Journal of Medicine “reassures on the continuation of their use“. “At 21 days after the booster dose, we found no evidence of an increased risk of cardiovascular events in recipients of the bivalent vaccine compared to recipients of the monovalent vaccine” explain the scientists. Who are the bivalent Covid vaccines intended for? In first vaccination? For the 3rd dose of vaccine? The 4th dose ? What is their efficiency ?
What is a bivalent vaccine?
A bivalent vaccine is a vaccine that has two valencies. A valence is the part of a vaccine corresponding to the protection against a single germ. A bivalent vaccine protects against 2 diseases or 2 germs causing the same disease. THE bivalent Covid vaccines thus protect against the initial strain of the Sars-CoV-2 coronavirus and against the Omicron variant of this virus. They have the same principle of action as monovalents: each contains mRNA (messenger RNA) molecules who have instructions for make the spike proteins of SARS-CoV-2 original and of the Omicron BA.1 or BA4-BA5 sub-variant. We can also have “multivalent” vaccines which protect against several germs causing the same disease or against different diseases (like the MMR vaccine which protects against measles, mumps and rubella).
Which bivalent vaccines are authorized in France?
- bivalent vaccine from Moderna (Original/Omicron BA.4-5 in single-dose vials)
- Moderna’s bivalent vaccine (Original/Omicron BA.1 in 5-dose vials)
- Comirnaty bivalent vaccine from Pfizer-BioNTech Original/Omicron BA.1
- Comirnaty bivalent vaccine from Pfizer-BioNTech Original/Omicron BA.4-5
What are Pfizer’s bivalent vaccines?
The bivalent Pfizer-BioNTech vaccines administered in France for booster doses are based on the original Covid vaccine, Comirnaty from Pfizer (the most administered in France since 2020). It is an RNA vaccine that targets the spike protein of SARS-CoV-2 and that of the Omicron BA4/BA5 sub-variant (or of the BA1 sub-variant). Other than the addition of the spike protein mRNA sequence, all other components of the vaccine are identical.
What are Moderna’s bivalent vaccines?
The American laboratory Moderna has also received authorization from the French authorities for the marketing of two bivalent vaccines: one targeting the BA.1 Omicron sub-lineage and the other the BA4-BA5 sub-lineage. These two vaccines cannot be used than in those over 30 (they are more highly dosed in RNA than that of Pfizer).
► The bivalent Omicron BA1 vaccine contains 25 mcg of the currently authorized booster And 25 µg of Omicron BA1 subvariant.
► The bivalent Spikevax Original/Omicron BA.4-BA.5 vaccine contains two mRNAs (mRNA-1273 present in the original monovalent vaccine (Wuhan strain) and mRNA-1273.045 present in the monovalent Omicron BA.4/BA.5 vaccine).
What are the side effects of bivalent Covid vaccines?
The tolerance of these vaccines “is identical to that of monovalent vaccines” said the HAS. Side effects observed with vaccines targeting Omicron were “comparable to those seen with the original vaccines and were generally mild and short-lived” has for its part indicated the EMA. Re Moderna’s bivalent vaccine, it “did not show any concerning side effects” completed Public Health France on October 26. The most frequent local and systemic adverse events found after injection of the original bivalent Spikevax vaccine/BA.1 as a second booster dose reported by the HAS are there injection site pain (77.3%), fatigue (54.9%), headache (43.9%), myalgia (39.6%), arthralgia (31.1%), as well as axillary swelling or tenderness (17.3%).
What is the risk of stroke with the Pfizer vaccine?
In January 2023, the Center for Disease Control and Prevention in the United States alerted the public to a possible increased risk of ischemic stroke within 21 days of the injection of the bivalent vaccine of Pfizer in people 65 or older. French researchers wanted to assess whether the risk of such events differed after receiving the bivalent booster compared to the monovalent booster. Their findings were published in April 2023 in The New England Journal of Medicine And “reassure on the continuation of their use“. “At 21 days after the booster dose, we found no evidence of an increased risk of cardiovascular events in recipients of the bivalent vaccine compared to recipients of the monovalent vaccine” explain the scientists. Their study was conducted on French vaccinations registered for 1 month between October and November 2022.
For who ?
These new Covid vaccines are aimed at people at risk of severe forms of Covid. They are authorized in people aged 12 and over who have received at least one primary vaccination course against Covid-19 (from the age of 30 for Spikevax), regardless of the vaccines then used. They are authorized only for a booster dose. The population groups to be targeted for this additional dose of vaccine according to HAS recommendations are:
- people over 60 and adults under 60 at risk of severe disease :
- those who have comorbidities that expose them to these severe forms,
- pregnant women, from the 1st trimester of their pregnancy,
- immunocompromised people regardless of age,
- children and adolescents at high risk suffering from pathologies justifying it.
- the entourage of these people (cocooning strategy) as well as the people who are in regular contact with them:
- professionals in the health and medico-social sector.
For people under 30HAS maintains its recommendation to only use Comirnaty® vaccines (Pfizer BioNTech).
Are bivalent vaccines authorized for primary vaccination?
No, in France, bivalent vaccines are only authorized for booster shots, not for primary vaccination.
How effective are bivalent vaccines?
To date, the efficacy of bivalent vaccines has only been analyzed on mice (when they are administered as a booster 7 months after the primary vaccination), not in population studies. “In the current context, previous vaccines remain effective against severe forms, hospitalizations and deaths. However, bivalent vaccines are better suited to circulating variants, and may contribute to vaccine efficacy against infection” estimated Public Health France on October 26, recognizing that “preliminary results are encouraging” but that they “must be confirmed in population studies”. For the WISE (Strategic Advisory Group of Experts on Immunization of WHO), “the data is not sufficient to favor them over others booster vaccines”. The monovalent vaccines used so far as a booster are as effective as the bivalent against the variants of Covid currently circulating, according to these experts. The important thing, they say, is to do a booster dose 4 to 6 months after the last to be protected.
Sources
Stroke, Myocardial Infarction, and Pulmonary Embolism after Bivalent Booster, NEJM, April 13, 2023.
Risk analysis on emerging variants of SARS-CoV-2 carried out jointly by Public Health France and the CNR Respiratory infection virus Update of 26/10/2022, n°33
Highlights from the Meeting of the Strategic Advisory Group of Experts (SAGE) on Immunization – October 3-6, 2022.
Launch of the autumn vaccination campaign against Covid-19, September 28, 2022, DGS.
Covid-19: HAS includes bivalent vaccines in the vaccination strategy for the fall. Press release, September 20, 2022
ECDC-EMA statement on booster vaccination with Omicron adapted bivalent COVID-19 vaccines. EMA. September 6, 2022.
Pfizer and BioNTech Receive Positive CHMP Opinion for Omicron BA.1-Adapted Bivalent COVID-19 Vaccine Booster in European Union. Pfizer, September 1, 2022
EMA CHMP adopts positive opinion recommending authorization for the use of Moderna’s Omicron-Targeting Bivalent Booster in the European Union, Moderna, September 1, 2022.