Clinical trial NCT05655351: Effect of a Vaccination Against COVID-19 on Monocyte Production of Oxygenated Derivatives.
Official title: How Does Vaccination Against COVID-19 Affect Monocyte Production of Oxygenated Derivatives ?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: CORONAVIRUS INFECTIONS
Keywords: COVID-19
Coronavirus
Anti-SARS-CoV-2 Vaccine
Reactive Oxygen Species
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2022-12-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a pilot observational, single-center study with prospective longitudinal follow-up.

Type of study: Non-Health Product. Category according to the Jarde law : Interventional research involving human subjects with minimal risks and constraints, Category 2.
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients under 30 years old before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 0
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients under 30 years old after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 7
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients under 30 years old after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 14
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients under 30 years old after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 28
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged 30 - 60 before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 0
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged 30 - 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 7
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged 30 - 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 14
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged 30 - 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 28
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged over 60 before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 0
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged over 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 7
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged over 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 14
measure: Monocyte production of oxygenated derivatives (Reactive oxygen species) in patients aged over 60 after anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 28
Secondary outcomes:
measure: A) Plasma AngII level before anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged under 30
timeFrame: Day 0
measure: A) Plasma AngII level before anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 0
measure: A) Plasma AngII level before anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged over 60
timeFrame: Day 0
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged under 30
timeFrame: Day 7
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 7
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged over 60
timeFrame: Day 7
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged under 30
timeFrame: Day 14
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 14
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged over 60
timeFrame: Day 14
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged under 30
timeFrame: Day 28
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 28
measure: A) Plasma AngII level after anti-SARS-CoV-2 vaccination with an mRNA vaccine in patients aged over 60
timeFrame: Day 28
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) before anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 0
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) before anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 0
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) before anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 0
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 7
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 7
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 7
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 14
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 14
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 14
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 28
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 28
measure: B) DNA lesion rate (%) and intensity in peripheral blood mononuclear cells (PBMC) 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 28
measure: C) Rate of T cell apoptosis before anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 0
measure: C) Rate of T cell apoptosis before anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 0
measure: C) Rate of T cell apoptosis before anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 0
measure: C) Rate of T cell apoptosis 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 7
measure: C) Rate of T cell apoptosis 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 7
measure: C) Rate of T cell apoptosis 7 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 7
measure: C) Rate of T cell apoptosis 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 14
measure: C) Rate of T cell apoptosis 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 14
measure: C) Rate of T cell apoptosis 14 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 14
measure: C) Rate of T cell apoptosis 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged under 30
timeFrame: Day 28
measure: C) Rate of T cell apoptosis 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged 30 - 60
timeFrame: Day 28
measure: C) Rate of T cell apoptosis 28 days after anti-SARS-CoV-2 mRNA vaccination in patients aged over 60
timeFrame: Day 28
measure: D) Presence of lymphopenia before anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged under 30
timeFrame: Day 0
measure: D) Presence of lymphopenia before anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 0
measure: D) Presence of lymphopenia before anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged over 60
timeFrame: Day 0
measure: D) Presence of lymphopenia 7 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged under 30
timeFrame: Day 7
measure: D) Presence of lymphopenia 7 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 7
measure: D) Presence of lymphopenia 7 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged over 60
timeFrame: Day 7
measure: D) Presence of lymphopenia 14 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged under 30
timeFrame: Day 14
measure: D) Presence of lymphopenia 14 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 14
measure: D) Presence of lymphopenia 14 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged over 60
timeFrame: Day 14
measure: D) Presence of lymphopenia 28 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged under 30
timeFrame: Day 28
measure: D) Presence of lymphopenia 28 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged 30 - 60
timeFrame: Day 28
measure: D) Presence of lymphopenia 28 days after anti-SARS-CoV-2 vaccination by an mRNA vaccine in patients aged over 60
timeFrame: Day 28
measure: E) Quantification of anti-S antibodies in patients aged under 30 before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 0
measure: E) Quantification of anti-S antibodies in patients aged 30 - 60 before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 28
measure: E) Quantification of anti-S antibodies in patients aged over 60 before anti-SARS-CoV-2 vaccination with an mRNA vaccine.
timeFrame: Day 28
measure: F) Constitution of a biobank
timeFrame: Day 28
Other outcomes:
Locations:
city: Nîmes
country: France
facility: CHU de Nîmes, Hôpital Universitaire Caremeau
Study officials:
References:
citation: Kundura L, Gimenez S, Cezar R, Andre S, Younas M, Lin YL, Portales P, Lozano C, Boulle C, Reynes J, Vincent T, Mettling C, Pasero P, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Loubet P, Sotto A, Tran TA, Estaquier J, Corbeau P. Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19. J Allergy Clin Immunol. 2022 Sep;150(3):594-603.e2. doi: 10.1016/j.jaci.2022.06.020. Epub 2022 Jul 14.