This is an open label, Phase IIa, controlled human malaria infection (CHMI) study aimed to assess whether the new vivax malaria vaccines ChAd63 PvDBP and MVA PvDBP can protect against malaria infection. The participants will receive one or two doses of ChAd63 PvDBP followed by one dose of MVA PvDBP 8 weeks later. Approximately 4 weeks after the second vacccination, the volunteers will be challenged (deliberately infected) with malaria by intravenous injection blood-stage
Volunteers will be recruited and vaccinated at the CCVTM, Oxford. There will be two groups vaccinated in the trial, with an optional third group included if fewer than 6 volunteers complete group 2. Up to 19 volunteers will be included in total. These will be compared to a matched number of infectivity controls, receiving no vaccination, who will be recruited as part of a separate study (VAC069 - NCT03797989).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
16
one dose of 5 x 10\^10 vp ChAd63 PvDBP and one dose of 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen.
Centre for Clinical Vaccinology & Tropical Medicine
Oxford, Oxfordshire, United Kingdom
Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects
Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between Groups 1, 2 and 3 (pooled data) and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.
Time frame: 3 months post CHMI
Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers
No of participants reporting adverse event
Time frame: Within 28 days following each vaccination. Vaccinations occurred at 0 and 2 months in Groups 1 and 3 (ChAd63, MVA PvDBP); and at 0, 17 and 19 months in Group 2 (ChAd63, ChAd63, MVA PvDBP).
The Humoral Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen
Total IgG antibody response to the P. vivax Duffy-binding protein (PvDBP)
Time frame: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3; and at 19 months in Group 2.
The Cellular Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen
PvDBPII-specific CD4+ CD45RA- CCR7- effector memory T cells producing IFN-γ
Time frame: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3 ; and at 19 months in Group 2.
Immunological Readouts for Association With a Reduced Parasite Multiplication Rate
Statistical correlation between anti-PvDBP antibody responses induced by the ChAd63 and MVA PvDBP vaccines and PMR.
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Time frame: 3 months post CHMI