The effectiveness of COVID-19 vaccines in reducing the risk of severe COVID-19 iscurrently demonstrated. In France, since the beginning of the vaccination campaign,54,266,859 people have received at least one injection (ie. 80.5% of the totalpopulation), 53,354,698 people now have a complete vaccination schedule (ie. 79.1% of thetotal population) and since the beginning of the booster campaign, 39,558,416 people havereceived a 1st booster dose.However, the data currently available on the persistence of immunity on the one hand, andthe appearance of viral variants with reduced sensitivity to vaccine immunity on theother, suggest the need to administer booster doses at variable intervals depending onage and comorbidities. Real-life efficacy data from France and around the World confirmthat people who have received a booster dose are better protected than those who haveonly received a primary vaccination schedule (HAS).In this context, the Ministry of Health, has pronounced on the possibility ofadministering a second booster dose for people aged 60 and over. Moreover, therecommendations for the Haute Autorité de Santé for the 2nd booster dose in generalpopulation should be available in June 2022.Three vaccines, mRNA BNT162b2 vaccine, Sanofi/GSK monovalent D614 and B.1.351formulations were administered as 1st booster in the CoviBOOST trial. All three vaccinesboosted antibodies and neutralizing response after a BNT162b2 initial course.Heterologous boosting with the Sanofi/GSK SARS-CoV-2 recombinant adjuvanted proteinvaccine B.1.351 (Beta formulation) provided higher rates of neutralizing antibodiesagainst variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine. Due tothe start of the study after the beginning of booster vaccination campaign in elderly,the enrollment of participants over 65 years of age was difficult so, only 8 subjectsaged 60 years and over were enrolled. As vaccine immunogenicity is lower in olderpopulations and is waning more rapidly, it is important to evaluate the adjuvantedvaccine in this population.The objective of this ancillary study is to compare, in participants aged of 60 years andolder and previously vaccinated with 3 doses of mRNA vaccine (2 doses of Pfizer BioNTech)and a 3rd dose of Pfizer BioNTech or Moderna, the immunogenicity of a second booster doseof the B.1.351 strain recombinant protein- based subunit vaccine to BNT162b2 (mRNA PfizerBioNTech Vaccine).These results will provide important information for boostervaccination recommendations in this age group.
The data currently available on the persistence of immunity on the one hand, and the
appearance of viral variants with reduced sensitivity to vaccine immunity on the other,
suggest the need to administer booster doses at variable intervals depending on age and
comorbidities. Real-life efficacy data from France and around the World confirm that
people who have received a booster dose are better protected than those who have only
received a primary vaccination schedule (HAS).
Currently available data from the United States and the United Kingdom show that the
protection conferred by the first booster dose diminishes after 3 months, particularly in
persons 60 years of age and older, and justified the recommendation of a second booster
dose.
Data from Israel show that a second booster dose (4th dose) reduces the rate of confirmed
infections by a factor of 2 and the rate of severe disease by a factor of 4. The safety
data, although limited, are reassuring.
In this context, the Ministry of Health, has pronounced on the possibility of
administering a second booster dose for people aged 60 and over. Moreover, the
recommendations for the Haute Autorité de Santé for the 2nd booster dose in general
population should be available in June 2022.
The vaccines currently recommended in France, for booster vaccination are mRNA vaccines.
However, some vaccines that were developed later in the clinic could present an
interesting alternative in terms of reactogenicity, accessibility, cost and
acceptability. Moreover, a heterologous vaccination scheme could be more immunogenic than
a homologous scheme. Therefore, it is important to be able to evaluate these vaccines as
a second booster dose.
The COVID 19 vaccines developed by Sanofi are based on a classical adjuvanted recombinant
protein approach. Three candidate vaccines are under development, one based on the Spike
protein of the SARS CoV-2 D614 strain, the other on the B.1.351 strain, and the third is
a vaccine combining the two.
Three vaccines, mRNA BNT162b2 vaccine, Sanofi/GSK monovalent D614 and B.1.351
formulations were administered as 1st booster in the CoviBOOST trial. All three vaccines
boosted antibodies and neutralizing response after a BNT162b2 initial course.
Heterologous boosting with the Sanofi/GSK SARS-CoV-2 recombinant adjuvanted protein
vaccine B.1.351 (Beta formulation) provided higher rates of neutralizing antibodies
against variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine.
Due to the start of the study after the beginning of booster vaccination campaign in
elderly, the enrollment of participants over 65 years of age was difficult so, only 8
subjects aged 60 years and over were enrolled. As vaccine immunogenicity is lower in
older populations and is waning more rapidly, it is important to evaluate the adjuvanted
vaccine in this population.
The objective of this ancillary study is to compare, in participants aged of 60 years and
older and previously vaccinated with 3 doses of mRNA vaccine (2 doses of Pfizer BioNTech)
and a 3rd dose of Pfizer BioNTech or Moderna, the immunogenicity of a second booster dose
of the B.1.351 strain recombinant protein- based subunit vaccine to BNT162b2 (mRNA Pfizer
BioNTech Vaccine).These results will provide important information for booster
vaccination recommendations in this age.
Participants enrolled will be healthy adults of 60 years old and over they will be
recruited in 15 centers in mainland France, via the COVIREIVAC network.
The study will be a randomized, single-blinded, multicentre trial with two parallel arms:
ARM 1 receiving Pfizer-BioNTech vaccine
- Group 1.A: 1rst booster Pfizer
- Group 1.B: 1rst booster Moderna
ARM 2 receiving SP/GSK subunit B.1.351 vaccine
- Group 2.A: 1rst booster Pfizer
- Group 2.B: 1rst booster Moderna
Participants will undergo 4 visits :
- V1 (D0): inclusion, randomization, pregnancy test, PCR test, blood draw and
administration of the booster dose
- V2 (D15): follow-up visit with a review of solicited and unsolicited local and
systemic reactions that occurred since the last visit, and blood draw
- V3 (D28): follow-up visit with review of potential adverse events and blood draw
- V4 (D90): follow-up visit with review of potential adverse events and blood draw
- V4 (D180): follow-up visit with review of potential adverse events and blood draw
Blood samples will be used to conduct immunological analyses, and cellular analyses for a
sub-category of 25 participants per group.
Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech)
In participants previously vaccinated with 3 doses of mRNA vaccine, he/she will receive
one dose of Comirnaty® (Pfizer-BioNTech) vaccine as a second booster
Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
In participants previously vaccinated with 3 doses of mRNA vaccine, he/she will receive
one dose of CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK vaccine as a second
booster
Inclusion Criteria:
1. Age ≥ 60 years.
2. Adult in good health or with a stable health status if pre-existing medical history.
Stable health status is defined as an existing disease that has not required a
significant change in treatment or hospitalisation for worsening in the 3 months
prior to inclusion, and for which no significant change in treatment or
hospitalisation for worsening of the disease is envisaged in the near future.
3. For participants over 60 years of age who participated in Coviboost, to have
received a booster dose of mRNA vaccine (Pfizer-BioNTech) administered at least 6
months before the 2nd booster dose
4. Not included in Coviboost (new participants to be recruited) and having received 2
doses of mRNA vaccine (Pfizer-BioNTech) with an interval of 3 to 6 weeks and a 1st
booster dose of mRNA vaccine (Pfizer-BioNTech) or Moderna administered at least 6
months before the 2nd booster dose
5. Understands and agrees to comply with the study procedures.
6. Written informed consent signed by the participant and the investigator.
7. Person affiliated to a social security scheme.
Exclusion Criteria:
1. Acute febrile infection (body Acute febrile infection (body temperature ≥ 38.0°C)
within the previous 72 hours and/or had symptoms suggestive of COVID-19 within the
last 28 days or had case contact within the last 10 days before the inclusion visit.
2. Virologically documented (PCR or serology) history of COVID 19.
3. Immunosuppressive drugs such as corticosteroids at a dosage > 10 mg prednisone
equivalent/day (excluding topical preparations and inhalers) within 3 months prior
to inclusion or within 6 months for chemotherapies.
4. Treated with immunoglobulin or other blood product within 3 months prior to
inclusion or scheduled for administration of immunoglobulin or blood product before
the end of the study.
5. Known HIV, HCV or HBV infection.
6. Any condition, such as cancer, that may reduce the immune response.
7. Use of experimental Ig, experimental monoclonal antibodies or convalescent serum is
not allowed during the study.
8. History of severe adverse reactions after vaccine administration including
anaphylactic reaction and associated symptoms such as rash, difficulty breathing,
angioedema and abdominal pain, or a history of an allergic reaction that may be
exacerbated by a component of the SARS-COV-2 vaccine during the first vaccine
injection.
9. Participant having been vaccinated against BCG in the previous year.
10. Having received a vaccination within 2 weeks prior to the 2nd booster dose or
scheduled to receive a licensed vaccine 2 weeks after the 2nd booster dose.
11. Any bleeding disorder considered as a contraindication to an intramuscular
injection, previous phlebotomy or receipt of anticoagulants.
12. Participation in other research involving humans (French classification Jardé 1 or
Jardé 2) within 4 weeks prior to the inclusion visit, or participation in any other
vaccine trial.
13. Subject under legal protection (e.g. guardianship, tutorship).
GH Broca-Cochin-Hôtel-Dieu CIC 1417 Cochin-Pasteur
Paris, France
Odile Launay, Principal Investigator
Assistance Publique - Hôpitaux de Paris