PpPfs25/ISA51 and ScPvs25/ISA51 Vaccines for Malaria
Condition: Plasmodium Falciparum; Plasmodium Vivax Malaria
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional
Phase: Phase 1

Summary: 
      This study, conducted at Johns Hopkins University Center for Immunization Research in
      Washington DC, will test the safety and immune response of healthy volunteers to two
      experimental malaria vaccines. Malaria is a disease of red blood cells caused by a parasite
      that spreads from person to person by mosquitoes. It affects people of all ages, but is
      particularly severe in children. Patients may have a high fever, chills and muscle aches.
      They sometimes can have severe complications that may even result in death.

      The vaccines in this study are called "transmission blocking" vaccines. These vaccines
      stimulate the person's immune system to produce antibodies against malaria. When a mosquito
      bites a vaccinated person, it ingests some of the person's blood. The antibodies in the
      ingested blood stop the malaria parasite from developing inside the mosquito. The mosquito
      would not be able to transmit malaria to other people. PpPfs25/ISA51 (Vaccine A) stimulates
      production of antibodies against the malaria parasite Plasmodium falciparum, and
      ScPvs25/ISA51 (Vaccine B) stimulates antibodies against the malaria parasite Plasmodium
      vivax. The vaccines also contain a substance called Montanide ISA51, which boosts the immune
      response to the vaccine.

      Healthy volunteers between 18 and 50 years of age may be eligible for this study. Candidates
      are screened with a medical history, physical examination, and blood and urine tests. Women
      who are able to become pregnant have a urine pregnancy test before each immunization.

      Participants are randomly assigned to receive two injections, spaced 4 months apart, of
      either Vaccine A or Vaccine B at one of three doses-high, medium, or low. Two subjects in
      each dose group additionally serve as "controls" and receive only Montanide ISA51 mixed with
      saline. The vaccine is injected into the muscle of the upper arm. Subjects are monitored for
      30 minutes after each injection for possible side effects and take home a diary card to
      record their temperature and any symptoms that may appear over the next 13 days.

      A blood sample is drawn before and on several occasions after each vaccination to check the
      subject's health and to evaluate the immune response to the vaccine. At 1, 3, 7, 14, and 21
      days after each vaccination, participants come to the clinic for a check of vital signs
      (temperature, pulse, respiration, and blood pressure), brief physical examination, and
      history of symptoms since the previous visit.
    

Detailed description: 
      The purpose of this Phase 1 clinical trial is to evaluate the safety, reactogenicity and
      immunogenicity of two malaria transmission-blocking vaccines, PpPfs25 and ScPvs25, in healthy
      adult volunteers. Of the four species of malaria that infect humans, Plasmodium falciparum is
      responsible for the majority of these deaths. However, outside of Africa, most of the malaria
      is caused by Plasmodium vivax; although these cases result in few deaths, they represent a
      major cause of morbidity and lead to a significant impact on the quality of life. The
      development of a safe and effective vaccine that prevents the transmission of P. falciparum
      or P. vivax would be an important addition to the current methods for controlling the spread
      of malaria parasites. A vaccine designed to prevent oocyst development in the mosquito by
      eliciting transmission-blocking antibodies in the vertebrate host would protect other
      individuals in the vicinity from becoming infected from the immunized person. Thus, despite
      no immediate role in personal protection, transmission-blocking vaccines are a potentially
      powerful component of a multifaceted public health approach to controlling or eliminating
      malaria. This study will be conducted at the Johns Hopkins University - Bloomberg School of
      Public Health, Center for Immunization Research. Seventy-two healthy male and non-pregnant
      female volunteers ages 18-50 will be enrolled. This study will be single blinded (to
      volunteers) and placebo-controlled. The study will evaluate three dose levels of both the
      PpPfs25 and ScPvs25 malaria vaccines (5 microg, 20 microg, 80 microg) emulsified with
      Montanide ISA51 as compared to Montanide ISA51 given alone. Seventy-two volunteers (60
      vaccine and 12 placebo) will be enrolled and assigned to one of six cohorts. In each cohort,
      10 volunteers will receive vaccine and 2 will receive placebo. Volunteers will be vaccinated
      by intramuscular injection on days 0 and 120. The groups will be staggered such that adequate
      safety evaluation can be performed prior to dose escalation. The duration of the study is 18
      months per volunteer. The primary objectives of this trial are to assess and compare, in a
      dose-escalating study, the safety and reactogenicity of the PpPfs25 and ScPvs25 transmission
      blocking vaccines as compared to adjuvant alone; and to assess and compare, in
      dose-escalating study, the duration of the antibody response over an 18 month period in each
      volunteer as well as the effect of boosting with a second vaccination at 4 months.
    

Intervention name(s): PpPfs25/ISA51 & ScPvs25/ISA51
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Human; Clinical Trial; Mosquito; Healthy Volunteer; HV