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Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults.
- Source :
-
PloS one [PLoS One] 2016 Oct 17; Vol. 11 (10), pp. e0163144. Date of Electronic Publication: 2016 Oct 17 (Print Publication: 2016). - Publication Year :
- 2016
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Abstract
- Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adolescent
Adult
Antibodies, Protozoan blood
Antibody Affinity immunology
Enzyme-Linked Immunosorbent Assay
Humans
Malaria Vaccines adverse effects
Malaria Vaccines chemistry
Malaria, Falciparum immunology
Malaria, Falciparum transmission
Microscopy, Fluorescence
Middle Aged
Pain etiology
Protozoan Proteins adverse effects
Protozoan Proteins chemistry
Protozoan Proteins genetics
Protozoan Proteins metabolism
Recombinant Proteins adverse effects
Recombinant Proteins biosynthesis
Recombinant Proteins chemistry
Vaccines, Conjugate immunology
Young Adult
Malaria Vaccines immunology
Malaria, Falciparum prevention & control
Plasmodium falciparum immunology
Protozoan Proteins immunology
Recombinant Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 11
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 27749907
- Full Text :
- https://doi.org/10.1371/journal.pone.0163144