Transmission-Blocking Vaccine Pvs230D1-EPA/Matrix-M in Healthy Malaria-Naive Adults Using a Plasmodium Vivax Controlled Human Malaria Infection and Transmission Model

• INCLUSION CRITERIA:

All Participants

In order to participate in this study, an individual must meet all of the following criteria:

• Age >=18 and <=54 years at the time of enrollment in this protocol, or for booster participants, at the time of enrollment into NIH protocol 001501.
• In good general health and without clinically significant medical history.
• Able to provide informed consent.
• Study comprehension exam passed (a score of >=80% or per investigator's discretion) prior to study activities.
• Individuals of childbearing potential must agree to use an acceptable method of contraception from 1 month prior to day 0 to 1 month after completion of anti-malarial treatment. Participants who receive only the booster vaccination need only agree to use contraception from 1 month prior to day 0 to 1 month after the booster vaccination.

Acceptable methods of contraception include the following:

• A barrier method (e.g., consistent condom use) combined with an oral contraceptive pill, hormonal patch, or ring.
• Parenteral hormonal contraceptive implant or an intrauterine device.

Participants who otherwise are not at risk of becoming pregnant, at the judgement of the investigator will not be required to use contraception. Such participants may include those:

• Having undergone hysterectomy, bilateral oophorectomy, or bilateral fallopian tube ligation.

• Having reached menopause (age >=45 years plus no menses for 12 consecutive months without an alternative medical cause).

• Having exclusive same-sex relations or committed longstanding abstinence due to a serious life choice.

• Having an exclusive male partner who has undergone vasectomy at least 4 months prior.

  • Suitable accommodation and reliable access to the NIHCC for the duration of the study, in the opinion of the investigator.
  • Willing to allow long-term storage of study samples for future research.

Primary Vaccine Series with CHMI-T Participants

In order to participate in this study an individual must meet all of the following criteria:

• RBCs positive for Duffy antigen/chemokine receptor.
• Willing to refrain from donating blood throughout the study until 3 years after completion of anti-malarial treatment.

Booster Vaccine Participants

In order to participate in this study an individual must meet all of the following criteria:

• Has received all 3 doses of the primary vaccine series as a part of NIH protocol 001501 with the 3rd dose occurring no less than 12 months prior to intended enrollment.
• Willing to refrain from donating blood throughout the study until 6 months after the booster vaccination.

The following additional criteria must be met in order to for participants to undergo optional CHMI-T:

• Willing to refrain from donating blood throughout the study until 3 years after completion of anti-malarial treatment.
• RBCs positive for Duffy antigen/chemokine receptor.

EXCLUSION CRITERIA:

All Participants

An individual who meets any of the following criteria will be excluded from participation in this study:

• Planned travel to a malaria-endemic area (see https://www.cdc.gov/malaria/travelers/country_table/a.html) until 6-months beyond the final vaccination.

  --Exceptions may be made, at the investigator s discretion, if the travel is limited to areas without appreciable levels of P. vivax transmission.

• History of travel to or residence in a P. vivax malaria endemic region for more than 2 weeks during the past 2 years.

• Any prior confirmed P. vivax malaria diagnosis or clinical history consistent with P. vivax malaria diagnosis within the previous 5 years, at the investigator s discretion.

• For individuals of childbearing potential:

  • Currently breastfeeding.
  • Currently pregnant as determined by history or a positive human choriogonadotropin (beta-hCG) test, urine or serum.
  • Planning to become pregnant in the next 12 months.

• History of anaphylaxis, severe allergy, or other concerning adverse reaction, in the opinion of the investigator, to a previous vaccine.

• Any individual without good peripheral venous access, at the investigator s discretion.

• Being a current or former study team member or clinical trial staff with direct involvement of the trial or being an employee supervised by a study team member.

• Any of the following within the specified periods:

  • 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).
  • Investigational or non-FDA approved/authorized product or vaccine within 28 days prior to study day 0, or
  • Prior receipt of packed red cells or other blood products or immunoglobulins within 6 months of study day 0, or
  • Receipt of any vaccination less than 28 days before day 0.

• Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history including:

  • Screening blood test laboratory parameters outside of local lab normal range.

    • Individuals may be included at the investigator s discretion for not clinically significant values outside of normal range.
    • In the event of abnormal test results, confirmatory repeat tests will be requested, at the investigator s discretion.

  • HIV, hepatitis B, and/or hepatitis C as determined by HIV antigen/antibody, Hepatitis B surface antigen, and anti-Hepatitis C antibody laboratory tests, respectively.

  • Immunodeficiency including asplenia or functional asplenia or significant autoimmune disease.

• Investigational P. vivax malaria vaccine within the last 2 years with the exception of Pvs230D1-EPA/MM as part of NIH protocol 001501.

• 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 participant s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.

Primary Vaccine Series Participants

An individual who meets any of the following criteria will be excluded from participation in this study:

• For individuals of childbearing potential:

  --Rh blood group negative.

• History of a severe reaction to arthropod bites, or history of anaphylaxis or severe unexpected allergy to any substance.

• Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history including:

  • Retinal disease, visual field changes, psoriasis, porphyria, or known allergy to chloroquine or artemether/lumefantrine.
  • Cardiac disease including >10% cardiovascular risk as determined by the nonlaboratory method described by Gaziano or an abnormal EKG demonstrating a corrected QT interval by Fridericia s (QTcF) formula of >450 msec or other concerning arrhythmia.

• Current or planned use of medications known to significantly prolong the QT interval or otherwise interfere with study agents.

• Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per day for the rest of the study (by attestation), at investigators discretion.

• History of alcohol use disorder (exceptions may be made at the investigator s discretion if they have completed treatment or are otherwise currently abstinent) or refusal to agree to refrain from drinking from the day of the challenge agent inoculation until completion of their antimalarial course.

Booster Vaccine Participants

An individual who meets any of the following criteria will be excluded from participation in the optional CHMI-T component of the study:

• For individuals of childbearing potential:

  --Rh blood group negative.

• History of a severe reaction to arthropod bites, or history of anaphylaxis or severe unexpected allergy to any substance.

• Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history including:

  • Retinal disease, visual field changes, psoriasis, porphyria, or known allergy to chloroquine or artemether/lumefantrine.
  • Cardiac disease including >10% cardiovascular risk as determined by the nonlaboratory method described by Gaziano or an abnormal EKG demonstrating a corrected QTcF of >450 msec or other concerning arrhythmia. For participants not undergoing CHMI-T after booster vaccine, no EKG will be required

• Current or planned use of medications known to significantly prolong the QT interval or otherwise interfere with study agents.

• Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per day for the rest of the study (by attestation).

• History of alcohol use disorder (exceptions may be made at the investigator s discretion if they have completed treatment or are otherwise currently abstinent) or refusal to agree to refrain from drinking from the day of the challenge agent inoculation until completion of their antimalarial course.

Co-enrollment guidelines: Co-enrollment in other trials is restricted. Consideration for coenrollment, other than enrollment on trials evaluating the use of an investigational malaria vaccine as described above will require the approval of the principal investigator. Study staff should be notified of co-enrollment on any other protocol.