Evaluation of the Protective Efficacy of a Vaccine Derived From the Synthetic CS Protein of Plasmodium Vivax
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a randomized, double-blind, controlled, which seeks to compare two groups of
      volunteers (naive and previously exposed to malaria) who were made 3 immunizations with a
      synthetic derivative of the CS protein of Plasmodium vivax in order to determine their
      protective efficacy. Then volunteers will be subject to an infectious challenge to assess the
      infectivity of gametocytes in the blood early stage of P. vivax in Anopheles albimanus
      mosquitoes.
    

Detailed description: 
      This study is a prospective controlled, blinded clinical trial, designed to establish the
      protective efficacy induced by the vaccine PvCSP between human volunteers with and without
      history of malaria.

      Study subjects

      This study will require the involvement of two types of volunteers:

        -  Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for
           experimental infection of mosquitoes, who will be enrolled in the endemic area.

        -  Volunteers for immunization: Two other groups of volunteers will be immunized with the
           vaccine PvCSP. A group of 16 people without previous exposure to malaria (naive) and
           another 16 people with a history of previous malaria infection (pre-immune).

      Methodology Recruitment of infected patients: Parasite donors will be recruited among P.
      vivax infected patients attending a diagnostic center in the endemic area.

      Infection of mosquitoes Blood from donors will be used to feed three days old mosquitoes by
      artificial membrane feeding technique. At day 7 a sample of mosquitoes will be examined to
      determine the degree of infection by dissection of the mosquito gut. On day 14, a small
      amount of mosquitoes with a good degree of infectivity will be used to infect challenged
      volunteers.

      Recruitment of pre-immune and naive volunteers: Volunteers for the immunization stage will be
      recruited both in the city of Cali, non-endemic region, and in Buenaventura, a malaria
      endemic region, through various activities such as conferences, meetings and other means
      approved by the IRB like posters and flyers.

      Immunization: Volunteers will be immunized with the vaccine (n=16) or placebo (n=16).

      Follow Up Volunteers will be under medical vigilance during the first hour following the
      immunization to detect any adverse reaction. After the first hour period a medical exam will
      be made. Eight hours after immunization, each volunteer will be telephoned to assess physical
      condition. Any adverse event (AE) will be registered.

      Subsequent follow up will be made on the day next to immunization and 1 or 2 weeks before the
      next immunization by a new clinical evaluation and AE report. Volunteers will be educated to
      contact the research staff at any moment.

      Infection of volunteers Immunized volunteers will be challenged on day ~150 of the study, 1
      month after the third immunization by the bite of 3±1 infected mosquitos. The "feeding cage"
      will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding
      window, wich will be covered by a mesh surface be placed against the volunteer's skin.

      Volunteers will be educated about the signs and symptoms of malaria and they will have a
      daily telephone contact during the first 6 days.

      Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily in
      order to establish the presence or absence of disease through thick blood smear and samples
      will be collected for retrospective real time PCR P. vivax.

      From day 23 until day 31, volunteers will receive physical and laboratory evaluation every
      other day and will have daily telephone contact.

      Once the patients present signs and symptoms of the disease curative treatment will be
      immediately provided, and 15 ml of blood will be drawn, which will be used for immune
      response assessment.

      If the volunteers do not develop the disease during the follow-up period, on day 31 they will
      be given antimalarial treatment.

      Treatment Volunteers will be treated with antimalarial drugs approved by the Colombian
      Ministry of Social Protection: chloroquine (three (3) doses: 600 mg initially, followed by
      450mg at 24, and 48 hours), associated with primaquine (30mg/día) for 14 days. All the
      volunteers will be asked to return two weeks after starting treatment for a thick blood smear
      test to ensure cure of malaria.
    

Intervention name(s): Vaccine PvCS N+C+R; Vaccine PvCS N+C; SSN Montanide ISA-51
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Vaccine PvCS N+C+R 60 mcg, freeze dried powder, Batch n°P0RGB, Exp: 18.10.2015 At month 2 and 6; Vaccine PvCS N+C 60 mcg, freeze dried powder, Batch n°P0RGA, Exp: 18.10.2015, at month 0; SSN Montanide ISA-51 1 mL
Intervention MeSH terms: Vaccines; Monatide (IMS 3015)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Malaria, vaccine, P. vivax