Background:Malaria is a disease carried by mosquitoes in tropical countries around the world. It cancause symptoms like fever, body aches, and weakness. More than half a million peopleworldwide died of malaria in 2021, mostly children. Researchers want to find ways toprevent the spread of this disease.Objective:To test the effects of a new malaria vaccine. (Volunteers will not be exposed tomalaria.)Eligibility:Healthy adults aged 18 to 50 years.Design:Volunteers will be screened. They will have a physical exam with blood and urine tests.They will take a short quiz to make sure they understand the study.Volunteers will have 3 visits to receive the vaccine. These visits will be about 1 monthapart. The vaccine will be injected into the muscle of the upper arm.Volunteers will have 12 additional clinic visits. These will start after the firstvaccine visit and continue for 8 months. The visits may include a physical exam and bloodtests. There will also be 7 follow-up phone calls. These will occur the day after eachvaccine visit and then continue for another 12 months. Participants will be asked howthey are doing and whether they have had any changes in their health.
Study Description:
Single-center, open-label, first-in-human, dose-escalating phase 1 study to characterize
the safety, immunogenicity, and transmission-blocking activity in healthy malaria-naive
adults of the Plasmodium vivax (P. vivax) transmission-blocking vaccine (TBV),
Pvs230D1-EPA combined with adjuvant Matrix-M (MM). Three doses of vaccine will be
administered at 1-month intervals (study days 0, 28, and 56). Subjects will be divided
into low, intermediate, and high dose groups based on the amount of the antigen component
in each vaccine dose:
- Group 1 (n = 10): 5 (micro)g Pvs230D1-EPA/50 (micro)g MM
- Group 2 (n = 10): 25 (micro)g Pvs230D1-EPA/50 (micro)g MM
- Group 3 (n = 10): 50 (micro)g Pvs230D1-EPA/50 (micro)g MM
Objectives:
Primary Objective
-To assess the safety and reactogenicity of Pvs230D1-EPA/MM in healthy malaria-naive
adults
Exploratory Objectives
- To determine the antibody response to Pvs230D1-EPA/MM
- To determine the functional response to Pvs230D1-EPA/MM by mosquito feeding assays
- To assess cellular and transcriptomic responses to Pvs230D1-EPA/MM
- To identify and characterize human monoclonal antibodies (mAbs) with activity
against Pvs230D1M
Endpoints:
Primary Endpoint
-Incidence and severity of local and systemic adverse events (AEs) or serious adverse
events (SAEs)
Exploratory Endpoints
- Anti-Pvs230D1M antibody levels as measured by enzyme-linked immunosorbent assay
(ELISA)
- Transmission-reducing activity (TRA) and/or transmission-blocking activity (TBA) of
Pvs230D1-EPA/MM using direct membrane feeding assays (DMFA)
- Cellular immune responses and whole genome transcriptional profiles
- Isolation of reactive antibodies from sorted B cells
Drug: Pvs230D1-EPA/Matrix-M
Pvs230 domain 1 (Pvs230D1) is a recombinant protein consisting of subdomain 1 of native
Pvs230 (Val-226 to Gly-427, Figure 2) produced in Pichia pastoris. The synthetic gene
sequence was optimized for P. pastoris expression and cloned into the expression vector
pPICZ(alpha)A, which also encodes a pre-prosecretory alpha-factor sequence.
- INCLUSION CRITERIA:
All of the following criteria must be fulfilled for a subject to participate in this
trial:
1. Age >=18 and <=50 years.
2. In good general health and without clinically significant medical history.
3. Able to sign a written informed consent prior to undertaking any study-related
procedure.
4. Vaccine comprehension exam completed, passed (a score of (Bullet)80% or per
investigator s discretion), and reviewed prior to enrollment.
5. Suitable accommodation and reliable access to the NIHCC for the duration of the
study, in the opinion of the investigator.
6. Individuals of childbearing potential must agree to use an acceptable method of
contraception from 1 month prior to enrollment to 1 month after the final
vaccination (i.e., from study day -28 until study day 84).
7. Individuals capable of fathering children must agree to use an acceptable method of
contraception from 1 month prior to enrollment to 1 month after the final
vaccination (i.e., from study day -28 until study day 84).
8. Willing to allow long-term storage of study samples for future research.
9. Willing to refrain from donating blood throughout the study until 6 months after the
last vaccination.
EXCLUSION CRITERIA:
A subject will be excluded from participating in this trial if any 1 of the following
criteria is fulfilled:
1. Planned travel to a malaria-endemic area until 6-months beyond the final vaccination
(see https://www.cdc.gov/malaria/travelers/country_table/a.html). Exceptions may be
made, at the investigator s discretion, if the travel is limited to areas without
appreciable levels of P. vivax transmission.
2. Any prior confirmed P. vivax malaria diagnosis or clinical history consistent with
P. vivax malaria diagnosis within the previous 10 years, at the investigator's
discretion.
3. Any subject without good peripheral venous access, at the investigator's discretion.
4. For individuals of childbearing potential:
1. Currently breastfeeding.
2. Currently pregnant as determined by history or a positive human
choriogonadotropin (beta-hCG) test.
5. Clinical trial staff with direct involvement in the conduct of the trial are
excluded from participation.
6. HIV, hepatitis B, and/or hepatitis C as determined by HIV antigen/antibody,
Hepatitis B surface antigen, and anti-Hepatitis C antibody laboratory tests.
7. Screening blood test or urinalysis laboratory parameters outside of local lab normal
range. Subjects may be included at the investigator s discretion for "not clinically
significant" values outside of normal range.
8. History of anaphylaxis, severe allergy, or other concerning adverse reaction, in the
opinion of the investigator, to a previous vaccine.
9. Any of the following within the specified periods:
1. Investigational P. vivax malaria vaccine within the last 2 years.
2. Chronic systemic immunosuppressive medications (>14 days) within 6 months of
study day 0 (e.g., cytotoxic medications, adrenocorticotrophic hormone, or
oral/parental corticosteroids equivalent to >0.5 mg/kg/day of prednisone).
Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids
for mild, uncomplicated dermatitis are allowed at the discretion of the
investigator.
3. Investigational or non-FDA approved/authorized product or vaccine within 28
days prior to study day 0.
4. Asplenia or functional asplenia.
5. Blood transfusion or IVIG within 6 months of study day 0.
10. Any other finding that, in the judgment of the investigator, would interfere with,
or serve as a contraindication to, protocol adherence, assessment of safety or
reactogenicity, or a subject s ability to give informed consent, or increase the
risk of having an adverse outcome from participating in the study.
Subjects who are excluded from participation for any of the reasons above may be
considered for
enrollment on a postponed schedule if the investigator considers this appropriate.
Subjects will be selected in an equitable manner from the available pool of potentially
eligible individuals, without regard to factors such as sex, gender, race, ethnicity,
socioeconomic status, etc., except for age.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Joel A Goldberg, M.D., Principal Investigator
National Institute of Allergy and Infectious Diseases (NIAID)