This Phase IIa/b randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the protective efficacy, safety, and immunogenicity of the PvCS/Montanide ISA-51 vaccine when followed by a controlled human malaria infection (CHMI) with Plasmodium vivax. The investigational product consists of synthetic peptides representing the central repeat and flanking regions of the P. vivax circumsporozoite (CS) protein formulated with the Montanide ISA-51 adjuvant. This vaccine formulation was selected based on earlier phase studies demonstrating acceptable safety and immune reactivity in adults.
The study will enroll 72 healthy adults aged 18-50 years residing in a malaria-endemic region of Chocó, Colombia. Participants will be randomized in a 2:1 ratio to receive either the PvCS/Montanide ISA-51 vaccine or placebo. Vaccinations will be administered intramuscularly at months 0, 2, and 4. Safety assessments will include clinical evaluations, laboratory monitoring, and systematic documentation of all adverse events throughout the vaccination and follow-up periods.
Immunogenicity will be characterized using standardized assays to quantify antibody responses (ELISA and indirect immunofluorescence) and cellular responses (ELISpot), including measurements of IFN-γ-secreting T cells. Samples will be collected at predefined time points to evaluate the magnitude, kinetics, and durability of immune responses.
Approximately one month after the third vaccination, participants will undergo CHMI via exposure to Anopheles albimanus mosquitoes infected with P. vivax sporozoites. The challenge will be conducted in a controlled setting with continuous clinical oversight. After CHMI, participants will undergo daily parasitological monitoring by thick smear, supplemented by PCR assays, until the detection of parasitemia or for up to 21 days post-challenge.
Participants who develop parasitemia will receive immediate antimalarial treatment according to national guidelines. Extended follow-up will include evaluations of treatment response, late-onset adverse events, and persistence of vaccine-induced immune responses for up to 12 months after CHMI.
The primary objectives are to determine whether vaccination with PvCS/Montanide ISA-51 reduces the risk of developing P. vivax parasitemia after CHMI and whether it prolongs the pre-patent period compared with placebo. Safety outcomes include the frequency and severity of local, systemic, and laboratory adverse events. Secondary objectives include detailed characterization of humoral and cellular responses and exploratory analyses assessing associations between immunogenicity and protection.
The study is expected to last approximately 30 months, including recruitment, immunization, challenge procedures, and follow-up. Results will provide critical data to guide future development of P. vivax CS-based vaccines and inform decisions regarding advancement to larger efficacy trials in endemic settings.
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