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Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.
- Source :
-
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2016 Feb 26; Vol. 10 (2), pp. e0004423. Date of Electronic Publication: 2016 Feb 26 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Background: A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.<br />Methods: We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.<br />Results: The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.<br />Significance: This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials.
- Subjects :
- Adolescent
Adult
Antibodies, Protozoan immunology
Female
Humans
Malaria Vaccines administration & dosage
Malaria Vaccines adverse effects
Malaria, Vivax immunology
Malaria, Vivax parasitology
Male
Middle Aged
Protozoan Proteins administration & dosage
Protozoan Proteins adverse effects
Vaccination
Young Adult
Malaria Vaccines immunology
Malaria, Vivax prevention & control
Plasmodium vivax immunology
Protozoan Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1935-2735
- Volume :
- 10
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS neglected tropical diseases
- Publication Type :
- Academic Journal
- Accession number :
- 26919472
- Full Text :
- https://doi.org/10.1371/journal.pntd.0004423