Study of the Humoral Response to SARS-CoV-2 Variants and of the Cellular Response After Vaccination Against COVID-19 in Immunocompromised People (COVIVAC-ID)
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|ClinicalTrials.gov Identifier: NCT04844489|
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : June 21, 2021
|Condition or disease||Intervention/treatment||Phase|
|Autoimmune or Autoinflammatory Diseases HIV Multiple Sclerosis Solid Tumors or Cancers Solid Organ Transplant||Other: Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19||Not Applicable|
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.184.108.40.206) 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||485 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Study of the Humoral Response to SARS-CoV-2 Variants and of the Cellular Response After Vaccination Against COVID-19 in Immunocompromised People|
|Actual Study Start Date :||April 16, 2021|
|Estimated Primary Completion Date :||April 16, 2023|
|Estimated Study Completion Date :||July 31, 2023|
Other: Blood samples for the study of the humoral response to SARS-CoV-2 variants and of the cellular response after vaccination against COVID-19
Blood samples at:
- Proportion of patients with a neutralizing antibody titer greater than 1/10 towards the wild strain and the English VOC 202012/01, South African 501Y.V2 variants and any other variants that may emerge [ Time Frame: At the third injection visit and at one, six and twelve months after the last injection ]
- Proportion of patients with a positive serology by detection of IgG anti-receptor-binding domain (RBD) antibodies to the Spike protein of SARS-CoV-2 measured by the SARS-CoV technique -2 IgG II Quant assay (Abbott) [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
- Proportion of patients with a positive serology by detection of the anti-Spike protein IgG antibodies of SARS-CoV-2 measured by the Euroimmun technique [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
- Proportion of patients with positive anti-RBD IgG serology on D0 [ Time Frame: At inclusion visit ]
- Anti-RBD IgG level [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
- Antibody neutralization title [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
- Neutralization title for antibodies against the wild strain and to the English VOC 202012/01, South African 501Y.V2 variants and any other variants that could be introduced to emerge. [ Time Frame: At second and third injection visits and at one, six and twelve months after the last injection ]
- Supervised and unsupervised analyzes of deep immunophenotyping of T and B lymphocytes [ Time Frame: At Day 0, at the third injection visit and at one month after the last injection ]Count of CD4 / CD8, B and NK T lymphocyte populations and quantification of Treg lymphocytes on fresh cells. In-depth immunophenotyping of T lymphocytes with naive distributions / memories and activation markers and on naive B distributions / memories and other classically described subpopulations
- Cytometric measurement of intracellular cytokines (IFN, TNF, IL-2, IL4, IL10, IL-17) after stimulation of T lymphocytes by pools of SARS-CoV-2, CMV, EBV and influenza peptides [ Time Frame: At Day 0, at the third injection visit and at one month after the last injection ]
- Structure and specificity of the TCR (T-cells Receptors) repertoire of blood cells [ Time Frame: At Day 0, at the third injection visit and at one month after the last injection ]High throughput TCR sequencing (Barennes et al, Nat Biotech, 2021) will be performed on separated CD8 and CD4 T cells. Standard diversity metrics, such as V and J gene usage, VJ combination and clonotype frequencies will describe the global repertoire structures before and after vaccination. TCR signatures that could characterize the immune response to vaccination will be define based on the dynamics of sequences. For such studies, analyses are based exclusively on the CDR3 region of the TCRs such as to analyze humans independently of their HLA genotype. Finally, we will search for virus specific TCRs using our curated database (Barennes et al, Nat Biotech, 2021)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04844489
|Contact: Anne-Geneviève MARCELIN, MD, PhDfirstname.lastname@example.org|
|Contact: Olivier BENVENISTE, MD, PhDemail@example.com|
|Hospital Pitié-Salpêtrière - AP-HP||Recruiting|
|Paris, France, 75013|
|Contact: Olivier BENVENISTE, MD,PhD 0142161088 firstname.lastname@example.org|