Monitoring of the Post-vaccination Immune Response to COVID-19 Among Hospital Staff (COVIDIM)

Vaccination against COVID-19 is a major public health issue to control the epidemic and reduce the number of severe infections and deaths. Three vaccines currently received use authorization in France: two mRNA vaccines and one recombinant viral vector vaccine. Immunogenicity data demonstrate that they induce the development of neutralizing antibodies and IgG directed against the viral S1 protein and the receptor binding domain (RBD). However, there are currently no data on the persistence over time of the humoral response induced by vaccination, and data are still incomplete on cellular immunogenicity. No immune correlate of protection has been established for COVID-19.

In addition, these data come from assays carried out with current vaccines developed against a lineage of SARS-CoV-2 known as wild type (without genetic mutations).

The main objective of this study is to monitor in hospital staff the temporal evolution of humoral immunity induced by anti-COVID-19 vaccines by using enzyme-linked immunosorbent assays (ELISA), at 3, 6, 12 and 24 months after the last injection of vaccine.

Study Overview

• Status: Recruiting
• Conditions: Hospital Staff; Vaccined Againt COVID-19
• Intervention / Treatment: Biological: Monitoring of the immune response

Detailed Description

• All medical, para-medical, medico-technical and administrative staff of the Clermont-Ferrand university hospital will be informed of the protocol through intra-hospital communication. The inclusion visit will be scheduled within 3 months +/- 14 days after the last injection of the vaccine. For volunteers who have not received their first injection, they will be offered to participate in the sub-study including an additional visit on the day of vaccination. They will be free to accept or refuse.
• As recruitment is consecutive, an anonymous list of potentially eligible subjects (with demographic data: age, sex; nature of the vaccine received) will be kept, in order to verify afterwards if the sample is representative.

• The study includes:

  1. Five visits over 21 months, 6 over 24 months for the subgroup included on the day of vaccination
  2. An interview with an investigator during the first visit, to collect the following data: hospital function, age, sex, weight, height, possible comorbidities exposing to a serious COVID-19 infection, possible COVID-19 infection prior to vaccination, date of vaccination and type of vaccine
  3. A self-questionnaire to update clinical data if necessary during the following visits

  4. A blood test at each visit, i.e. 2 tubes of 5 mL (antibody assays) and 4 tubes of 1 mL (cellular immunity assay).

     Blood samples will be stored at -80°C, before destruction at the end of the study.

• In the case of suspecting symptoms of COVID-19 during follow-up, molecular testing of SARS-CoV-2 infection will be offered and performed from nasopharyngeal swab or saliva sample.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Aura
    • Clermont-Ferrand, Aura, France, 63000
      • Recruiting
      • Clermont-Ferrand University Hospital
      • Principal Investigator: Cécile Henquell

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult person, man or woman, staff of the Clermont-Ferrand University Hospital (medical or paramedical, medico-technical or administrative caregiver), having received the second dose of vaccine (or the single dose if the single-dose vaccination schedule) against COVID- 19 3 months +/- 15 days before the inclusion visit, as part of the national vaccination campaign, regardless of the type of vaccine administered.
• For the subgroup included before vaccination (study of the pre-vaccination cellular response): Adult person, man or woman, staff of Clermont-Ferrand University Hospital (medical or paramedical, medico-technical or administrative caregiver), receiving the 1st injection on the same day or in the 7 days before the inclusion visit, regardless of the type of vaccine administered
• Commitment to respect the schedule of visits provided for in the research protocol
• Able to give informed consent to participate in research
• Affiliation to a social security scheme

Exclusion Criteria:

• Pregnancy or breastfeeding in progress at inclusion, or planned during follow-up
• Person under guardianship, guardianship or legal protection
• Whether the vaccine received was experimental or not authorized
• Refusal of participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Monitoring of the immune response; Immune response controlled with blood sample at 3, 6, 12, 18 and 24 months	Biological: Monitoring of the immune response; Blood sample at 3,6,12,18 and 24 months in order to assess the blood level of anti-S1 / RBD anticoprs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the blood level of anti-S1 / RBD antibodies	temporal evolution of humoral immunity induced by the anti-COVID-19 vaccine, at 3, 6, 12 and 24 months after the second injection (or the single injection if single dose vaccination schedule), using two quantitative enzyme-linked immunosorbent assays (ELISA) targeting anti-S1 and anti-RBD antibodies.	3 months
the blood level of anti-S1 / RBD antibodies	temporal evolution of humoral immunity induced by the anti-COVID-19 vaccine, at 3, 6, 12 and 24 months after the second injection (or the single injection if single dose vaccination schedule), using two quantitative enzyme-linked immunosorbent assays (ELISA) targeting anti-S1 and anti-RBD antibodies.	6 months
the blood level of anti-S1 / RBD antibodies	temporal evolution of humoral immunity induced by the anti-COVID-19 vaccine, at 3, 6, 12 and 24 months after the second injection (or the single injection if single dose vaccination schedule), using two quantitative enzyme-linked immunosorbent assays (ELISA) targeting anti-S1 and anti-RBD antibodies.	12 months
the blood level of anti-S1 / RBD antibodies	temporal evolution of humoral immunity induced by the anti-COVID-19 vaccine, at 3, 6, 12 and 24 months after the second injection (or the single injection if single dose vaccination schedule), using two quantitative enzyme-linked immunosorbent assays (ELISA) targeting anti-S1 and anti-RBD antibodies.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relationship between the level of antibodies detected by serological tests (ELISA) and the antibodies titrated using an in vitro neutralization test	Comparison of the humoral response evaluated by serological tests with that analysed by neutralisation in vitro, on pairs of samples chosen to cover the variability of the response induced by vaccination between M3 and M24.	3 months, 6 months, 12 months, 18 months, 24 months
anti-S lymphocyte response induced by the anti-COVID-19 vaccine	Cellular immune response induced by the anti-COVID-19 vaccine evaluated by the anti-S lymphocyte response reflected by the determination of IFN-γ at the 3rd, 6th, 12th, 18th and 24th months after the second injection of vaccine (or the single injection if scheme single dose vaccine).	3 months, 6 months, 12 months, 18 months, 24 months
effect of age on immune response	Study the effect of age on the various immune parameters studied, in general and in their temporal course	3 months, 6 months, 12 months, 18 months, 24 months
Intensity of immune response according to different comorbidities	Study the effect of comorbidities on the various immune parameters studied, in general and in their temporal course	3 months, 6 months, 12 months, 18 months, 24 months
Intensity of immune response according to a previous COVID-19 infection or not	Study the effect of a previous COVID-19 infection on the various immune parameters studied, in general and in their temporal course	3 months, 6 months, 12 months, 18 months, 24 months
Intensity of immune response according to the type of vaccine administered	Study the effect of the type of vaccine administered on the various immune parameters studied, in general and in their temporal course	3 months, 6 months, 12 months, 18 months, 24 months
the cellular immune response directed against the Spike peptides of T lymphocytes before vaccination, between D-7 and the day of the 1st injection of vaccine	Pre-vaccine anti-S cellular immune response reflected by the IFN-γ assay, for a subgroup of 50 volunteers then benefiting from the same follow-up until the 24th month	Day 1
genomic characteristics of the strain of SARS-CoV-2 in case of proven COVID-19 infection during follow-up	Clinical description of subjects presenting with COVID-19 infection during follow-up, and genomic characteristics of their strain of SARS-CoV-2 by whole genome sequencing (next-generation sequencing).	up to 24 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand

Publications and helpful links

General Publications

• Bonnet B, Chabrolles H, Archimbaud C, Brebion A, Cosme J, Dutheil F, Lambert C, Junda M, Mirand A, Ollier A, Pereira B, Regagnon C, Vidal M, Evrard B, Henquell C. Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers. Front Immunol. 2022 Mar 2;13:842912. doi: 10.3389/fimmu.2022.842912. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 21, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Humoral response to Covid-19 Vaccine; Cellular response to Covid-19 Vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: RBHP 2021 HENQUELL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No