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This is an open label phase Ia study, to assess the safety of two novel malaria vaccines, ChAd63 PvDBP, with or without MVA PvDBP. Heterologous prime-boost with ChAd63-MVA is, to our knowledge, one of the most potent T cell-inducing subunit vaccine regimens which can importantly also induce antibodies. Previous clinical trials using this regimen expressing ME-TRAP, AMA1 & MSP1, have shown that administering ChAd63 as a prime followed 8 weeks later by MVA as a boost is a very immunogenic schedule (32-34). For this reason, and to provide comparability with previous ChAd63-MVA trials, we propose to use a similar administration schedule.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | 4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^9 vp intramuscularly |
|
| Group 2A | Experimental | 4 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly |
|
| Group 2B | Experimental | 8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 1 x 10^8 pfu 8 weeks later intramuscularly |
|
| Group 2C | Experimental | 8 volunteers; 1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly and 1 dose MVA PvDBP 2 x 10^8 pfu 8 weeks later intramuscularly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ChAd63 PvDBP 5 x 10^9 | Biological | 1 dose of ChAd63 PvDBP 5 x 10^9 vp intramuscularly |
| |
| Measure | Description | Time Frame |
|---|---|---|
| The safety in healthy volunteers of two new candidate malaria vaccines, ChAd63 PvDBP administered alone, and with MVA PvDBP, in a prime-boost regime. | To assess the safety of ChAd63 PvDBP when administered alone and in heterologous prime-boost with MVA PvDBP. Safety will be assessed by the frequency, incidence and nature of adverse events and serious adverse events arising during the study as well as abnormalities in Hematology and Biochemistry lab tests. | Up to 20 weeks post first vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| The humoral and cellular immunogenicity of ChAd63 PvDBP, when administered to healthy volunteers alone and with MVA PvDBP. | PvDBP_RII-specific immunogenicity will be assessed by a variety of immunological assays. These may include ex vivo ELISpot assays for interferon gamma and flow cytometry assays, as well as antibody ELISAs. Other exploratory immunological assays including cytokine analysis, antibody assays, anti-adenovirus antibodies, DNA analysis of genetic polymorphisms potentially relevant to vaccine immunogenicity and gene expression studies amongst others may be performed at the discretion of the investigators. Other exploratory immunology may be carried out in collaboration with other specialist labs, including labs outside of Europe. This would involve transfer of serum/plasma, but samples will be anonymised. Volunteers will be consented beforehand. |
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Inclusion Criteria:
Agreement to refrain from blood donation during the course of the study.
-Provide written informed consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Adrian V S Hill, MD | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Clinical Vaccinology and Tropical Medicine | Oxford | Oxfordshire | OX3 7LE | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28614791 | Derived | Payne RO, Silk SE, Elias SC, Milne KH, Rawlinson TA, Llewellyn D, Shakri AR, Jin J, Labbe GM, Edwards NJ, Poulton ID, Roberts R, Farid R, Jorgensen T, Alanine DG, de Cassan SC, Higgins MK, Otto TD, McCarthy JS, de Jongh WA, Nicosia A, Moyle S, Hill AV, Berrie E, Chitnis CE, Lawrie AM, Draper SJ. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight. 2017 Jun 15;2(12):e93683. doi: 10.1172/jci.insight.93683. eCollection 2017 Jun 15. |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| D016780 | Malaria, Vivax |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ChAd63 PvDBP 5 x 10^10 |
| Biological |
1 dose of ChAd63 PvDBP 5 x 10^10 vp intramuscularly |
|
| MVA PvDBP 1 x 10^8 | Biological | 1 dose MVA PvDBP 1 x 108 pfu 8 weeks later intramuscularly |
|
| MVA PvDBP 2 x 10^8 | Biological | 1 dose MVA PvDBP 2 x 108 pfu 8 weeks later intramuscularly |
|
| U to 20 weeks post first vaccination. |
| D000079426 |
| Vector Borne Diseases |