Primary Outcome Measures:
- Part A Dose-escalation
- • Assess the safety and tolerability of NMRC-M3V-Ad-PfCA, in a dose-escalation design, in healthy, malaria-naïve adults.
- Part B Regimen-comparison
- Assess the safety and tolerability of the two components individually (NMRC-MV-Ad-PfC, NMRC-MV-Ad-PfA) and when combined (NMRC-M3V-Ad-PfCA).
- Assess the protective efficacy against sporozoite challenge (Pf, 3D7 strain) of the two components individually (NMRC-MV-Ad-PfC, NMRC-MV-Ad-PfA) and when combined (NMRC-M3V-Ad-PfCA).
Secondary Outcome Measures:
- Part A Dose-escalation
- • Assess the immunogenicity of NMRC-M3V-Ad-PfCA in healthy, malaria- naïve adults.
- Part B Regimen-comparison
- Assess immunogenicity of the two components individually (NMRC-MV-Ad-PfC, NMRC-MV-Ad-PfA) and when combined. (NMRC-M3V-Ad-PfCA)
- Compare immunogenicity and protective efficacy of one vs. two doses of NMRC-M3V-Ad-PfCA.
- Compare immunogenicity and protective efficacy of two doses of NMRC-M3V-Ad-PfCA administered at short (ten days) vs long (16 weeks) intervals.
The vaccine, called NMRC-M3V-Ad-PfCA (key: NMRC + Multi-antigen Multi-stage, Malaria Vaccine + Adenovectored + P. falciparum CSP & AMA1 antigens), is a combination of two recombinant adenovirus-derived constructs (adenovectors), one expressing the pre-erythrocytic stage antigen circumsporozoite protein (CSP) and the other expressing the erythrocytic stage antigen Apical Membrane Antigen 1 (AMA1), both from the 3D7 strain of P. falciparum. The vector is an attenuated, replication-deficient adenovirus derived from wildtype serotype 5 adenovirus through the deletion of several genes. The vaccine is formulated in a buffered saline solution (Final Formulation Buffer = FFB).
This is a Phase 1/2a, randomized, open-label, dose-escalating trial of the NMRC-M3V-Ad-PfCA vaccine administered intramuscularly to healthy, malaria-naïve adult volunteers. All volunteers will be seronegative (< 1:500, by a luciferase-based neutralizing antibody assay; VRC, Bethesda) for adenovirus serotype 5. In the first part of the study (dose-escalation phase, Part A), 1 x 1010 particle units (pu) per construct or 2 x 1010 pu total will be administered to six volunteers as a single dose to assess safety, and 4 weeks later, 5 x 1010 pu per construct or 1 x 1011 pu total dose (five-fold dose escalation) will be administered to six additional volunteers. In the second part of the study (regimen-comparison phase, Part B), three regimens for administration will be compared: one dose, two doses administered ten days apart, and two doses administered 16 weeks apart. Separate groups will receive one dose of the individual components of the vaccine (NMRC-MV-Ad-PfC and NMRC-MV-Ad-PfA). Following immunization, volunteers participating in the regimen-comparison phase as well as several non-immunized control volunteers (serving as infectivity controls) will be challenged with P. falciparum sporozoites in order to assess vaccine efficacy against non-immunized controls challenged at the same time. The proposed design of the regimen-comparison phase will provide information to direct selection of an appropriate dosing regimen for subsequent studies, and will also indicate whether the two constituent antigens, when co-formulated, act synergistically, independently, or interfere with each other in the induction of antigen-specific immune responses and protective immunity.