Effect of a Vaccination Against COVID-19 on Monocyte Production of Oxygenated Derivatives.

NCT ID: NCT05655351

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-21
• Study Completion Date: 2024-07-30

Brief Summary

Knowing that the vaccine antigen includes the ACE2 binding moiety (RBD), the hypothesis is that circulating vaccine antigen could reduce the enzymatic activity of ACE2, and thus increase circulating AngII concentration, monocyte ROS production and lymphocyte apoptosis. This hypothesis is supported by the fact that the Spike protein of SARSCoV-1, which uses the same receptor as SARS-CoV-2, induces a decrease in expression and activation of the Angiotensin II pathway in mice (Kuba et al. 2005).

Detailed Description

In this pandemic period, vaccination against SARSCoV- 2 is an essential weapon. However, the immune memory induced by current vaccines remains ephemeral, requiring early booster shots. It is primordial to improve this vaccine memory.

Recently it has been demonstrated that monocytes from certain individuals hospitalized for SARSCoV-2 infection spontaneously overproduced oxygenated derivatives (ROS) capable of inducing DNA damage in neighboring cells and T cell apoptosis (Kundura et al., 2022). In agreement with these observations, up to 50% of peripheral blood mononuclear cells (PBMC) from these patients showed DNA damage and its intensity was correlated with the percentage of apoptotic CD8+ T cells and lymphopenia.

Upon entry into the target cell, SARS-CoV-2 induces the internalization of its receptor, the protease Angiotensin Converting Enzyme 2 (ACE2), which is able to degrade Angiotensin II (AngII). Consequently, the circulating level of AngII was observed to be increased in some COVID-19 patients. It was also found that AngII induced monocyte ROS production via its receptor Angiotensin receptor 1 (AT1), making monocytes capable of damaging the DNA of co-cultured cells. Moreover, the plasma level of AngII in patients correlates with the level of ROS production and the ability to damage DNA of their monocytes. The level of anti SARS-CoV-2 antibodies was shown to be inversely correlated with the level of monocyte production of ROS production during the acute phase. This suggests that the activation cascade leading to lymphopenia described could damage the specific immune memory.

Now, a recent article has established the presence of circulating S1 vaccine antigen following the injection of an anti-SARS-CoV-2 vaccine with mRNA vaccine from D1 to D7 at a level of 68 ± 21 pg/mL (Ogata et al. 2022) similar to the level described in COVID-19 (Ogata et al. 2020). If the cascade of events we have identified is triggered by the circulation of the vaccine antigen, this could lead to could result in a reduced vaccine memory via lymphocyte apoptosis.

Knowing that the vaccine antigen includes the ACE2 binding moiety (RBD), the hypothesis is that circulating vaccine antigen could reduce the enzymatic activity of ACE2, and thus increase circulating AngII concentration, monocyte ROS production and lymphocyte apoptosis. This hypothesis is supported by the fact that the Spike protein of SARSCoV-1, which uses the same receptor as SARS-CoV-2, induces a decrease in expression and activation of the Angiotensin II pathway in mice (Kuba et al. 2005).

Conditions

CORONAVIRUS INFECTIONS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Patients vaccinated with the anti-SARS-Cov-2 vaccination

These patients will receive the anti-SARS-Cov-2 vaccination and their blood will be regularly monitored.

Group Type: EXPERIMENTAL

anti-SARS-Cov-2 vaccination

Intervention Type: BIOLOGICAL

For the purposes of the study, 10 mL of venous blood will be collected from each patient.

Interventions

anti-SARS-Cov-2 vaccination

For the purposes of the study, 10 mL of venous blood will be collected from each patient.

Intervention Type: BIOLOGICAL

Other Intervention Names

Blood test

Eligibility Criteria

Inclusion Criteria

• Candidate for SARS-CoV-2 vaccination with an mRNA vaccine (Pfizer, Moderna).
• Subject has given free and informed consent.
• Subject who has signed the consent form.
• Person affiliated to or beneficiary of a health insurance plan.

Exclusion Criteria

• Patients under treatment with N-acetylcysteine or sartan.
• Patients with a dysimmune pathology or immunosuppressive treatment.
• Person infected with SARS-CoV-2 within 3 months prior to inclusion.
• Person participating in a category 1 defined RIPH.
• Subject in an exclusion period as determined by another study.
• Person under court protection, guardianship or trusteeship.
• Subject who is unable to give consent.
• Subject for whom it is impossible to give clear information.
• Pregnant or breastfeeding woman.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Nîmes, Hôpital Universitaire Caremeau

Nîmes, France, France

Countries

France

References

Gimenez S, Hamrouni E, Andre S, Picard M, Soundaramourty C, Lozano C, Vincent T, Tran TA, Kundura L, Estaquier J, Corbeau P. Monocytic reactive oxygen species-induced T-cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine. J Allergy Clin Immunol. 2025 May;155(5):1635-1646. doi: 10.1016/j.jaci.2025.01.003. Epub 2025 Jan 10.

Reference Type: RESULT

PMID: 39800264 (View on PubMed)

Other Identifiers

2022-A02026-37

Identifier Type: OTHER

Identifier Source: secondary_id

NIMAO 2022-1

Identifier Type: -

Identifier Source: org_study_id