Epitope Mapping and Fine Specificity of Human T and B Cell Responses for Novel Candidate Blood-Stage Malaria Vaccine P27A.
- Geiger KM Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
- Guignard D Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
- Yang C Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Bikorimana JP Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Correia BE Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Houard S European Vaccine Initiative, Heidelberg, Germany.
- Mkindi C Swiss Tropical and Public Health Institute, Basel, Switzerland.
- Daubenberger CA Swiss Tropical and Public Health Institute, Basel, Switzerland.
- Spertini F Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Corradin G Biochemistry Department, University of Lausanne, Epalinges, Switzerland.
- Audran R Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- 2020-03-27
Published in:
- Frontiers in immunology. - 2020
English
P27A is a novel synthetic malaria vaccine candidate derived from the blood stage Plasmodium falciparum protein Trophozoite Exported Protein 1 (TEX1/PFF0165c). In phase 1a/1b clinical trials in malaria unexposed adults in Switzerland and in malaria pre-exposed adults in Tanzania, P27A formulated with Alhydrogel and GLA-SE adjuvants induced antigen-specific antibodies and T-cell activity. The GLA-SE adjuvant induced significantly stronger humoral responses than the Alhydrogel adjuvant. Groups of pre-exposed and unexposed subjects received identical vaccine formulations, which supported the comparison of the cellular and humoral response to P27A in terms of fine specificity and affinity for populations and adjuvants. Globally, fine specificity of the T and B cell responses exhibited preferred recognized sequences and did not highlight major differences between adjuvants or populations. Affinity of anti-P27A antibodies was around 10-8 M in all groups. Pre-exposed volunteers presented anti-P27A with higher affinity than unexposed volunteers. Increasing the dose of GLA-SE from 2.5 to 5 μg in pre-exposed volunteers improved anti-P27A affinity and decreased the number of recognized epitopes. These results indicate a higher maturation of the humoral response in pre-exposed volunteers, particularly when immunized with P27A formulated with 5 μg GLA-SE.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.3389/fimmu.2020.00412
- PMID 32210975
- Persistent URL
- https://sonar.ch/global/documents/172983
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