- To assess the in vitro memory T cell response to 20 therapeutic SARS-CoV-2 vaccine candidate synthetic long peptides (SLPs);- To assess the in vitro humoral immune response to 20 therapeutic SARS-CoV-2 vaccine candidate SLPs.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Memory T cell response as assessed by interferon-* enzyme-linked immune
absorbent spot (ELISpot) assay and/ or enzyme-linked immunosorbent assay
(ELISA) and intracellular cytokine staining (ICS) after stimulation of
peripheral blood mononuclear cells (PBMCs) with each of the 20 therapeutic
SARS-CoV-2 vaccine candidate SLPs
Secondary outcome
* Serum IgG antibodies as measured by ELISA against each of the 20 therapeutic
SARS-CoV-2 vaccine candidate SLPs
Background summary
In December 2019, a newly identified coronavirus, called severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in China causing
coronavirus disease-2019 (COVID-19). The rapid global outbreak of SARS-CoV-2
led the World Health Organization (WHO) to characterize COVID-19 as a pandemic.
Millions of people have been affected by the disease and worldwide incidence
and mortality are still increasing. At this moment, a tremendous amount of
research is being conducted in search of a potential prophylactic COVID-19
vaccine. Such vaccines may be deployed for widespread global immunization
programs to protect against COVID-19. Before a highly effective prophylactic
vaccine can be developed, licenced and become widespread available there
remains an unmet medical need for curative treatment modalities against
COVID-19. There is currently no proven curative treatment available against
COVID-19. Treatment with the licensed nucleoside analogue remdesivir reduces
hospitalization duration, but its effect on disease mortality and progressions
remains disputed. Current investigational therapeutics for COVID-19 mainly
focus on drugs with antiviral activity, immunomodulatory drugs or convalescent
plasma/antibodies, and prophylactic vaccines. Far less research effort has been
put into the development of a therapeutic vaccine for COVID-19. Such a
therapeutic vaccine can be administered after SARS-CoV-2 infection has occurred
and could in theory prevent subsequent (severe) disease by targeted
immunotherapy. Therapeutic vaccines against COVID-19 are therefore an
attractive treatment modality that warrants further investigation.
ISA Pharmaceuticals B.V. is developing a therapeutic vaccine against
SARS-CoV-2, called ISA106, for patients recently infected with SARS-CoV-2. This
vaccine is intended as a therapeutic modality as well as preventive for
patients at increased risk of severe illness from COVID-19 and related death,
such as older patients and patients with certain underlying diseases (eg,
diabetes). Severe patients appear to be characterized by an impaired T cell
immune response. This deficient T cell response may represent a relevant
therapeutic vaccine target.
The ISA106 vaccine is based on synthetic long peptides (SLPs) in order to boost
T cell immunity. SLPs are aimed to be taken up and processed by
antigen-presenting dendritic cells (DCs) before they are presented rather than
direct binding to major histocompatibility complex (MHC) class I molecules on
the cell surface. This should facilitate a stronger and more effective immune
response than with a vaccine based on exact MHC-binding peptides. SLPs are
degraded by DCs into antigenic protein fragments, called epitopes. These
epitopes can stimulate both CD4+ helper T cells and CD8+ T cells responses.
Potential ISA106 vaccine candidate epitope-rich SLPs were selected by
integrating different sources of available data. This included T cell epitope
predictions generated by predictive algorithms to identify candidate targets
for immune responses to SARS-CoV-2. This was combined with the observation that
SARS-CoV-2 is closely related to SARS-CoV that caused the severe acute
respiratory syndrome (SARS) outbreak in 2002-2004. Epitopes conserved among
both coronaviruses are considered promising targets for immune recognition of
SARS-CoV-2 and selected accordingly. The pool of potential T cell epitopes was
further refined by utilizing proprietary algorithms developed by ISA
Pharmaceuticals B.V. that also take into account the feasibility of producing
the epitope-rich SLPs under good manufacturing practice (GMP) conditions.
Furthermore, the actual T cell responses observed in COVID-19 patients and
epitopes predicted to elicit a IgG antibody response were considered. This
approach yielded 20 potential ISA106 vaccine candidate epitope-rich SLPs, each
of a length of 25-35 amino acids, together covering the anticipated most
immunogenic sequences of the spike (S), membrane (M) and nucleocapsid (N)
proteins of SARS-CoV-2.
Before ISA106 will be taken into phase 1 clinical testing, the elicited immune
response to the SLPs should be characterized in vitro to guide to the final
selection of most immunogenic SLPs. The current study is intended to stimulate
blood from recovered COVID-19 patients and healthy controls in vitro with the
current 20 candidate SLPs. This study is essential for the determination of the
final ISA106 vaccine composition.
Study objective
- To assess the in vitro memory T cell response to 20 therapeutic SARS-CoV-2
vaccine candidate synthetic long peptides (SLPs);
- To assess the in vitro humoral immune response to 20 therapeutic SARS-CoV-2
vaccine candidate SLPs.
Study design
This is an exploratory study that is part of the development trajectory of a
therapeutic SARS-CoV-2 vaccine. A total of 14 subjects will be enrolled: 10
recovered COVID-19 patients and 4 healthy controls. The study will consist of a
single visit, the total duration of the study for each subject will not be more
than half a day. During the visit, subject*s eligibility for this study will be
assessed prior to sample collection and blood will collected for the study
endpoints.
Study burden and risks
No investigational drug will be administered to the volunteers. The invasive
procedures under this protocol will be restricted to blood sample collection
(venipuncture). The burden for the volunteer related to the study procedures is
limited. Only well-established methods of sample collection will be applied,
with a known and limited risk and no or mild discomfort for the volunteer. In
addition, all collections will be performed by qualified medical staff.
No clinical benefit can be expected from this study for the participating
subjects.
J.H. Oortweg 19
Leiden 2333 CH
NL
J.H. Oortweg 19
Leiden 2333 CH
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for both recovered COVID-19 patients and healthy participants
1. Participant must sign the study informed consent form prior to any
study-mandated procedure indicating that he or she understands the purpose,
procedures and potential risks, and is willing to participate in the study;
2. Participant is male or female and between 18 and 65 years of age, inclusive,
at the time of enrollment;
3. Participant is willing and able to complete the study procedures;
4. Participant has a primary care physician at the time of enrollment;
5. Participant is not taking any immunosuppressive medication or other
immunomodulating agents (including investigational drugs) for at least 3 weeks
prior to study blood sampling.
Inclusion criteria for recovered COVID-19 patients only
1. Participant reports a previous positive diagnostic test result for
SARS-CoV-2 infection (serological testing or viral RNA detection by PCR
testing);
2. Participant had clinical symptoms of COVID-19 (including, but not limited
to: cough, fever, shortness of breath, sudden onset of anosmia, ageusia or
dysgeusia). The diagnosis of COVID-19 must be the most plausible cause of the
reported symptoms, as deemed by the study physician;
3. Participant has recovered from COVID-19 for at least three weeks prior to
study blood sampling (residual symptoms such as, but not limited to, fatigue
and reduced exercise tolerance - that would not jeopardize study endpoints -
are allowed at the investigator*s discretion).
Inclusion criteria for healthy participants only
1. Participant is generally healthy in the investigator*s clinical judgment, as
determined by medical history evaluation, including no clinically significant
disorder, condition, infection or disease that would interfere with the study
evaluation, procedures or completion.
Exclusion criteria
Exclusion criteria for both recovered COVID-19 patients and healthy participants
1. Participant with a whole blood donation or loss of >500 ml within 21 days
before study blood sampling;
2. Any known factor, condition, or disease that might interfere with
compliance, study conduct or interpretation of the results, as deemed by the
investigator.
Exclusion criteria for healthy participants only
1. Participant reports a previous positive diagnostic test result for
SARS-CoV-2 infection (serological testing or viral RNA detection by PCR
testing);
2. Participant developed clinically overt symptoms of COVID-19 following close
contact with a proven SARS-CoV-2 positive patient, but was not tested (e.g. due
to limited test capacity and regulations at that time);
3. Participant who is currently working, or has worked in an occupation with a
high risk of exposure to SARS-CoV-2 (e.g. health care worker).
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL74814.058.20 |