BNT162b2 Vaccination With 2 Doses in COVID-19 Negative Volunteers and With a Single Dose in COVID-19 Positive Volunteers

A Phase II Trial Assessing Immunogenicity and Safety of COVID-19 mRNA Vaccine BNT162b2 in Adult Volunteers With no History of SARS-CoV-2 Infection Administered With Two Doses of Vaccine (D1-D29) and in Adult Volunteers With Documented History of SARS-CoV-2 Infection (of More Than 5 Months) Administered With Only One Dose of Vaccine

As previously shown, individuals who experienced COVID-19 have developed some protective immunity to reinfection. The magnitude and duration of protection from reinfection conferred by the infection may be weaker after an asymptomatic infection as it is after a symptomatic COVID-19 episode. Moreover, it is known that immunity decreases among older adults compared to younger individuals often referred to as ''immune senescence,'' and leading to a decreased efficacy of vaccination.

This study raises the question of whether a single administration of BNT162b2 in participants with prior SARS-CoV-2 infection leads to sufficient and durable immune response.

We propose to evaluate the level of the single BNT162b2 vaccine dose response according to the severity of the previous SARS-CoV-2 infection in young and elderly participants with the same immunogenicity analyses to assess this response in participants receiving the two-dose vaccination regimen.

This is a national open phase II trial, assessing the immunogenicity and safety of vaccine candidate Pfizer - BNT162b2 against SARS-CoV-2 in participants with no history of SARS-CoV-2 infection receiving two doses of vaccine and in participants with history SARS-CoV-2 infection of more than 5 months and receiving only one dose of vaccine.

A total of 300 volunteers will be included and vaccinated in 2 groups:

Group 1: Adults with no history of SARS-CoV-2 infection(N=150)

• Sub-group 1A: 18 - 45 years old: 50 volunteers
• Sub-group 1B: 65 - 74 years old: 50 volunteers* (minimum of 45)
• Sub-group 1C: At least 75 years old: 50 volunteers* (minimum of 45)

Group 2: Adults with history of SARS-CoV-2 infection of more than 6 months (N=150)

• Sub-group 2A: 18 - 45 years old: 50 volunteers
• Sub-groupe 2B : 65 ans et plus: 100 participants

Within each subgroup of the group 2, a distribution will be respected including:

• 1/3 volunteers with asymptomatic COVID-19 infection,
• 1/3 volunteers with mild COVID-19 infection ((symptomatic but not hospitalized or hospitalized but no oxygen required) and
• 1/3 volunteers with severe COVID-19 infection (hospitalization and oxygen required).

Participants within the group 1 will receive BNT162b2 (Comirnaty®) intramuscularly as a 2-dose series spaced 28 days apart at a dose of 30 µg each, then a booster dose (30µg) at M8.

Participants within the group 2 will receive BNT162b2 intramuscularly as a single dose of 30 µg, then a booster dose (30µg) at M8.

Analyses of humorale and saliva immune responses will be performed in differents centralized laboratories blinded for the trial group, by ELISA at Day -6/D0 (pre-vaccination sample), D29, D57, M6, M12, and M24.

T and B cell analyses will be performed in a sub-group of participants Immunosenescence will be analysed in pre-vaccination samples.

Inclusion Criteria:

1. 18 to 45 years old or at least 65 years old,

2. Healthy adults or stable medical condition for adults with pre-existing medical conditions. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during 3 months before enrolment, nor expected to require any significant change in therapy or hospitalization for worsening disease in foreseeable future.

3. Group 1: Healthy adults with no previous history of SARS COV2 infection (PCR-, antigenic test- or chest TDM- or serology SARS-CoV-2-) Group 2: Healthy adults with history of infection with SARS COV 2 (PCR+, antigenic test+ or chest TDM+ or serology SARS-CoV-2 of more than 5 months) OR have been a household contact subject and have presented COVID-19 symptoms [Experienced at least TWO of the following systemic symptoms: Fever (≥ 38ºC), chills, myalgia, headache, sorethroat, new olfactory and taste disorder(s), gastrointestinal symptoms (diarrhea and/or vomiting) or at least ONE of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographical evidence of pneumonia] since at least 5 months ago and have had a positive SARS-CoV-2 serology between this episode and pre-inclusion.

4. A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

   • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile. OR
   • Is of childbearing potential and agrees to use an effective contraceptive method from at least 4 weeks prior to vaccination until at least 4 weeks after the last vaccination. A participant of childbearing potential must have a negative blood pregnancy test at enrolment visit.

5. Understands and agrees to comply with the study procedures (visits, phone calls) based on Investigator judgement

6. Written and informed consent signed by the person and the investigator (no later than the day of pre-inclusion and prior to any examination realized in the frame of the trial) (article L1122-1-1 of the Public Health Code)

7. Affiliated or beneficiary of a social security scheme (article L1121-11 of the Public Health Code) (AME is not a social security scheme)

8. who agrees to be registered in the national file of persons who lend themselves to biomedical research (article L1121-16 of the Public Health Code).

Exclusion Criteria:

1. Participant is ill or febrile (body temperature ≥ 38.0°C) within 72 prior hours or and/or symptoms suggestive of COVID-19 or being contact subject within the past 14 days at enrolment visit.

   (Ill or febrile participants may be re-scheduled within the trial inclusion period when no longer presenting symptoms, except if condition is COVID19)

2. Participants with positive PCR, antigenic test or chest TDM or serology to SARS-CoV-2 at the enrolment visit, only for the group1.

3. Participants who already received another anti-SARS-CoV-2-vaccine

4. Participants who received BCG given within the last year.

5. Use of immunosuppressive drugs like e.g. corticosteroids at a dosage > 10mg equivalent prednisone /day (excluding topical preparations and inhalers) within 3 months prior to enrolment or 6 months for chemotherapies

6. Received immunoglobulin or other blood product within 3 months prior to enrolment or planned receipt of immunoglobulin or a blood product through study completion.

7. Received any vaccination within 4 weeks prior to first injection or plan to receive a licensed vaccine within 4 weeks after the last injection.

8. History of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as rash, respiratory difficulty, laryngeal oedema and abdominal pain to vaccines, or history of allergic reaction likely to be exacerbated by any component of the anti-SARS-CoV-2-vaccine.

9. History of severe allergic event

10. Known HIV, active HCV or HBV infection

11. Any pathological condition, such as cancer, which may be susceptible of reducing immunity response

12. Any bleeding disorder considered as contraindication to intramuscular injection or phlebotomy

13. The use of investigational Ig, investigational monoclonal antibodies or convalescent serum are not allowed during the study

14. Any condition which in the opinion of the investigator may interfere with the aim of the study

15. Pregnant or breastfeeding or positive pregnancy blood test at enrolment visit.

16. An immediate family member or household member of study staff.

17. Participation in another investigational clinical study (Jardé 1 or Jardé 2) within 4 weeks before the enrolment visit or still in an exclusion period from another clinical trial or participation in another investigational clinical study planned before the study completion.

18. People under legal protection measure (tutorship, curatorship or safeguard measures)