Target Antigens Induced by Plasmodium Falciparum Sporozoite Immunization Under Chemoprophylaxis
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional

Summary: 
      Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious
      diseases. With approximately 627.000 deaths a year, there is desperate need for an effective
      vaccine. Though a number of vaccine-candidates have been developed, they have yet to achieve
      the level of efficacy necessary to eliminate malaria. It has been shown previously that
      healthy human volunteers bitten by malaria-infected mosquitoes while taking chloroquine,
      medicine that prevents malaria, are fully protected against a subsequent malaria challenge.
      This is called CPS-immunization. The unprecedented effectiveness of CPS-immunization makes it
      a good model to identify what immune responses protect against malaria, to further guide
      vaccine development. In this study we will use CPS-immunization to induce protection against
      malaria in healthy subjects and then analyse their immune response to a malaria challenge
      infection.
    

Detailed description: 
      Rationale:

      Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious
      diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and
      mortality as well as a significant contribution to ongoing poverty in endemic countries.
      Ultimately, the key to malaria control and hopefully eradication, would be an effective
      vaccine. Though a number of vaccine-candidates have entered the pipeline of pre-clinical and
      clinical development, they have yet to achieve the level of efficacy necessary for effective
      malaria prevention. It has been shown previously that healthy human volunteers can be fully
      protected against malaria infection with a homologous parasite by immunization with
      Plasmodium parasites while taking chloroquine chemoprophylaxis (ChemoProphylaxis and
      Sporozoites, CPS-immunization). The unprecedented efficacy of CPS-immunization makes it a
      unique model to identify pre-erythrocytic target antigens for the development of a subunit
      vaccine. Identification of antigens that play a significant role in the development of
      sterile protection against malaria will provide a basis for the development and evaluation of
      more effective sub-unit candidate vaccines.

      Primary objective:

      • To delineate the antibody repertoire directed against the pre-erythrocytic stages of
      Plasmodium falciparum induced by CPS-immunization.

      Secondary objectives:

        -  To assess the functionality of CPS-immunization induced antibodies.

        -  To determine T-cell antigen specificities in CPS-immunized, protected volunteers.

      Exploratory objectives:

        -  To assess the functionality of CPS-immunization induced T-cells.

        -  To explore the adaptive and innate immune responses during CPS-immunization and early
           malaria infection.

      Study design:

      This is a single-centre, randomized open-label study. A total of 15 volunteers will be
      divided into two groups, one scheduled to receive CPS immunization (Group 1, n=10) and one to
      receive only chloroquine prior to malaria challenge (Group 2, n=5).

      Study population:

      The study population will be comprised of male and female healthy subjects. A total of 15
      subjects will be enrolled to participate in the study and randomized.

      Intervention:

      In the immunization group a total of four CPS immunizations will be performed, with 15 bites
      from Plasmodium infected mosquitoes per immunization, over a period of four months, during
      which volunteers will take chloroquine prophylaxis. The control group will take only
      chloroquine prophylaxis during this period. All volunteers will undergo Controlled Human
      Malaria Infection (CHMI) by exposure to 5 bites from Plasmodium falciparum sporozoite
      infected mosquitoes.
    

Intervention name(s): CPS-immunization; Controlled Human Malaria Infection; chloroquine; atovaquone/proguanil
Intervention type(s): Biological; Biological; Drug; Drug
Intervention description(s): Subjects will receive four 'immunizations' with bites from 15 Plasmodium infected mosquitoes during each immunization, while taking chloroquine prophylaxis.; Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum, NF54 strain.; Registered for prophylaxis against infection with Plasmodium falciparum and the treatment of acute infections.; Registered for use as an antimalarial agent for the treatment of acute infections with Plasmodium falciparum.
One tablet contains: atovaquone 250 mg, proguanil(hydrochloride) 100 mg
Other intervention name(s): Plasmodium falciparum NF54 infected Anopheles mosquitoes; Chloroquine; Plasmodium falciparum NF54 infected Anopheles mosquitoes; Malarone
Intervention MeSH terms: Chloroquine; Chloroquine diphosphate; Atovaquone; Proguanil; Atovaquone, proguanil drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: malaria; Plasmodium falciparum