Immune Response
Conditions
Keywords
Trained immunity, Innate immune system, MV130, Sublingual vaccine, Trained immunity-based vaccines
Brief summary
A mechanistic clinical trial with the aim to evaluate whether MV130 can induce the expression of a particular immune response (trained immunity) in peripheral blood cells. Therefore, the investigators are not evaluating efficacy in any disease or medical condition but rather assessing the immunological effect in immunogenicity of MV130 in healthy volunteers.
Detailed description
Bacillus Calmette-Guérin (BCG) has been postulated as a strategy to prevent transmission and reduce the incidence of infectious diseases due to its ability to induce trained immunity. However, it is not recommended to vaccinate with live-attenuated vaccines, such as BCG, to certain vulnerable populations including immunocompromised patients. This issue can be overcome with inactivated preparations that mediate trained immunity such as MV130. The safety of MV130 in pilot studies in patients with immunodeficiency or solid organ recipients, has been highlighted in recent studies. Based on the principles of trained immunity, it has recently been suggested that this concept can be further exploited in a next generation of anti-infectious vaccines: Trained immunity-based vaccines (TIbV). Thus, these vaccines may confer a broad protection far beyond to the nominal antigens they contain.
Interventions
BIOLOGICALMV130
Treatment administered sublingually
OTHERPlacebo
Treatment administered sublingually
Sponsors
Inmunotek S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Randomization will be done in a 1:1 ratio in blocks of 6, through a random list. It will be impossible for investigators to know to which group a subject will be assigned before being included in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects that have provided written informed consent. * Healthy males and females 18 to 65 years, both included, at the time of enrolment. * Subjects who are able to provide cooperation and comply with dosing regimen. * Women of childbearing age (from menarche) should submit a urine pregnancy test with a negative result at the time of enrolment in the trial.
Exclusion criteria
* Simultaneous participation in another clinical trial. * Females who are pregnant or breast-feeding, or potential pregnant or breast-feeding females. * Subjects who are allergic to any of the components included in MV130. * Subjects with any concomitant disease or treatment that, according to the investigator criteria, may affect the development of this study, such as immunodeficiencies, malignancies involving bone marrow or lymphoid systems, medical treatment affecting the immune system (including corticosteroids, immunosuppressants, biological agents,…), human immunodeficiency virus, severe allergies, diabetes, hypertension, psychological disorders, etc. * Subjects who have been vaccinated within 12 months before inclusion (flu or any other vaccine different from COVID-19 vaccine), or who have planned to be vaccinated during the clinical study (excluding the COVID-19 vaccine). * Subjects who have had an infection that included fever and/or diarrhoea within 3 months before inclusion. * Subjects under metformin treatment during the last month before inclusion in the clinical study or during the clinical trial\*. * Subjects under statins treatment during the last month before inclusion in the clinical trial or during\*. \*: these drugs interfere with metabolic pathways involved in trained immunity induction. * Subjects who are allergic to any of the components included in the flu vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase ex vivo in cytokine response | 70 days | The primary outcome is the increase ex vivo in cytokine response (TNF-alfa, IL-6 and/or IL-1beta) in PBMCs upon secondary restimulation (MV130, lipopolysaccharide \[LPS\], inactivated Candida albicans, Resiquimod-R848, Poly I:C and/or phytohemagglutinin \[PHA\]) in MV130 vaccinated subjects compared to placebo group, at days 15, 45 and/or 70, with respect to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in percentages of immune populations in peripheral blood including T and B cells, NK cells and subsets of monocytes, in MV130 group compared to placebo at days 15, 45 and/or 70, with respect to baseline. | 70 days | Changes in percentages of immune populations in peripheral blood including T and B cells, NK cells and subsets of monocytes, in MV130 group compared to placebo at days 15, 45 and/or 70, with respect to baseline. |
| Change in MV130 non-specific response (T and B cells from PBMCs) in MV130 treated group compared to placebo. | 70 days | It includes T cell proliferation (days 15, 45 and/or 70) by labelling T cells with carboxyfluorescein succinimidyl ester (CFSE) prior to restimulation with PHA, inactivated C. albicans and flu antigens. Also, change of cytokine production (such as IFN-gamma, IL-17 and/or IL-10) from T cells upon restimulation (LPS, inactivated Candida albicans, flu antigens and/or PHA) (days 15, 45 and/or 70 with respect to baseline). It also includes antibody production: cross-reactive serum IgG against viral components. Different viral proteins/peptides will be tested (days 45 and 70 with respect to baseline). Antibody responses against flu antigens (IgG and IgA in serum and IgA in saliva) will be evaluated (days 45 and 70 with respect to baseline). |
| MV130 specific response (T and B cells responses form PBMCs) in MV130 vaccinated group compared to placebo. | 70 days | It includes T cell proliferation and cytokine production (IFN-gamma, IL-17 and/or IL-10) following restimulation with MV130 (days 15, 45 and/or 70 with respect to baseline). It also includes antibody production: MV130 specific IgG and IgA levels in serum and IgA levels in saliva (days 45 and/or 70 with respect to baseline). Individual bacteria contained in MV130 (i.e., S. pneumoniae) will be further tested for specific antibody production. |
| Change in baseline oral microbiota composition in MV130 treated group (days 45 and 70 with respect to baseline) compared to placebo, based on the 16S rRNA sequence phylogeny. | 70 days | Change in baseline oral microbiota composition in MV130 treated group (days 45 and 70 with respect to baseline) compared to placebo, based on the 16S rRNA sequence phylogeny. |
| Rates of adverse events | 70 days | The overall rate of adverse events in both groups |
| Classification of the Adverse events | 70 days | Classification of the Adverse events during the trial |
| Epigenetic and metabolic changes in purified monocytes from PBMCs, in a subgroup of MV130 vaccinated (n=12) versus placebo (n=12), at day 45 with respect to baseline. | 70 days | It includes specific miRNA associated to trained immunity (miR155, miR146 and/or miR21, etc.) and histone marks (H3K4me3 and/or H3K27me3, among others), as epigenetic rewiring markers. It also includes lactate production, glucose consumption and mitochondrial activity as metabolic changes. |
| Classification of the Adverse reactions | 70 days | Classification of the Adverse reactions during the trial |
| Percentage by type of adverse events | 70 days | Percentage by type of adverse events occurred during the trial |
| Percentage of subject with adverse reactions | 70 days | Percentage of subject experiencing adverse reactions during the trial |
| Timing of reaction appearance | 70 days | Time from the first administration to appearance of the reaction |
| Classification of the adverse reaction according to the place of appearance | 70 days | Classification of the adverse reaction in local or systemic, depending on the place of appearance |
| Rates of adverse reactions | 70 days | The overall rate of adverse reactions in both groups |
Countries
Spain
Contacts
Primary ContactMiguel Casanovas Verges, MD, PhD
Outcome results
None listed