Prospective, multicenter, non-comparative cohort study of immunocompromised people vaccinated against Covid-19 with the aim to know the humoral and cellular response to BNT162b2 vaccination against SARS-CoV-2 variants. This study will enroll patients in 5 parallel sub-cohorts of the same size, distinct according to the source of the immunosuppression: autoimmune or auto-inflammatory disease, HIV infection, multiple sclerosis, solid cancer, organ transplantation with prospective data collection and constitution of biological collections.

The SARS-CoV-2 pandemic represents an extraordinary challenge for global health, it has caused more than 97 million cases of Covid-19 and 2 million deaths worldwide as of January 22, 2021. Vaccination against Covid-19 is an essential weapon to mitigate the consequences of the SARS-CoV-2 pandemic. Its effect in reducing mortality is of course expected in people most vulnerable to Covid-19 such as immunocompromised people.

In general, the immunogenicity of vaccines in immunocompromised populations is conditioned by the nature and intensity of the chronic pathology (s), the age and the treatments received. In addition, the emergence of new variants of SARS-CoV-2 is a major concern today. Three new variants that have rapidly become dominant within their countries have aroused concerns: B.1.1.7 (also known as VOC-202012/01), 501Y.V2 (B.1.351), and P.1 (B.1.1.28.1) and questions are raised about their potential to escape from vaccine-induced immunity. It is therefore important to be able to assess vaccine efficacy in subjects who are fragile with respect to these variants.

The investigators are proposing the establishment of a multicenter cohort study of immunocompromised people vaccinated against Covid-19 with the aim to know the humoral and cellular response to BNT162b2 vaccination against SARS-CoV-2 variants. The primary objective is to evaluate the neutralizing capacity of the antibodies regarding different variants of SARS-CoV-2 after vaccination on 1 month after the first injection, then on 1, 6 and 12 months after the last injection. In-depth immunophenotyping of immune blood cells which analyzes in detail the subpopulations of T lymphocytes and their responses to SARS-CoV-2 will be also analyze before vaccination and after vaccination on 1 month after the first injection, then on 1 month after the last injection. Extensive explorations of the humoral and cellular response to BNT162b2 vaccination will provide crucial data on the potential efficacy of the BNT162b2 vaccine on the recently identified SARS-CoV-2 variants, as well as innovative data on the dynamic of the functional responses of T cells and of the TCR repertoire, the dynamic of which (increase after vaccination, remote contraction) makes it possible to link them to a vaccine response, as has already been done in the context of other vaccination.

This study will provide a better understanding of the biological response to BNT162b2 vaccination in immunocompromised people with respect to the English VOC 202012/01, South African 501Y.V2 variants and any other variants that may emerge. In particular, the investigators are waiting to be able to estimate the proportion of patients whose immunogenicity suggests a reduction in the frequency of severe forms of COVID-19. Conversely, the investigators are waiting to estimate the proportion of patients with a level of immunogenicity too low to hope for good clinical protection against COVID-19. In addition, there are no data on the durability of the biological response to BNT162b2 vaccination.

It is possible that these observations could lead to the implementation of reinforced vaccination protocols for this population, as is already the case for vaccination for hepatitis B vaccination.

Inclusion Criteria:

• Age greater than or equal to 18 years

• Patients eligible for BNT162b2 vaccination

• Immunocompromised patients according to one of the following criteria:

  1. Patients with autoimmune or autoinflammatory diseases treated

     1. For at least three months
     2. Having received at least 0.1 mg / kg / day of prednisone (or equivalent) for at least three months
     3. Currently receiving at least 5 mg / day of prednisone in combination with an immunosuppressant (methotrexate, cyclosporine, mycophenolate mofetil, rapamycin, azathioprine, cyclophosphamide) or biotherapy (anti-B cells (rituximab and others) anti-TNF, IL- 1, IL-6R, IL-12/23, IL-17, or B7 (CTLA4-Ig)) or a kinase inhibitor (Janus, Tyrosine))

  2. HIV-infected patients with a CD4 count <500 / mm3 and a viral load <50 copies / ml on stable antiretroviral therapy for at least 3 months

  3. Patients with multiple sclerosis treated with a disease-modifying drug for at least 3 months at a stable dose (teriflunomide, dimethyl-fumarate, fingolimod, ocrelizumab, rituximab, natalizumab)

  4. Patients with solid tumors or cancers:

     1. Patients who have received active cancer treatment other than chemotherapy (targeted therapy, radiotherapy, surgery, hormone therapy) in the previous month
     2. Patients who have received active cancer treatment with chemotherapy (alone or in combination with immunotherapy, radiotherapy or targeted therapy) in the previous month
     3. Patients who have received active oncology treatment with one or more immunotherapy (s) in combination with anti-PD1, anti-PD-L1, anti-CTLA4 antibodies without chemotherapy in the previous month.

  5. Solid organ transplant patients for more than 3 months who have not received a depleting T agent in the induction protocol, and for> 6 months otherwise

• Life expectancy of more than 3 months

• Having been informed about the study and having given their written and informed consent

• Beneficiaries or beneficiaries of a social security scheme

Exclusion Criteria:

• Patients who may be included in more than one of the sub-cohorts
• Other vaccination received in the 15 days preceding recruitment or planned in the month following the second vaccine injection
• Known or suspected allergy to one of the components of the vaccine
• Severe reaction after previous administration of any influenza vaccine (multiple sclerosis, Guillain-Barré syndrome)
• Contact subjects of a patient with an undetected documented SARS-CoV-2 infection
• Evocative signs of COVID-19
• History of documented SARS-CoV-2 infection of less than 3 months (RT-PCR, Lamp PCR, antigen test)
• Last outbreak of the disease less than 3 months old for patients with Multiple Sclerosis; less than a month old for patients with autoimmune or autoinflammatory diseases
• For patients with HIV, transient viremia (blip) less than 3 months old
• Intercurrent infection
• For organ transplants, episode of cellular or humoral rejection during the 3 months preceding inclusion
• Healthy volunteers
• Pregnancy less than 13 weeks old according to the declaration of pregnancy
• Refusal of participation by the patient
• Patients subject to legal protection measures