Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
| Autor: | Erik Jongert, Richard H. C. Huntwork, S. Munir Alam, Milite Abraha, Sheetij Dutta, S. Moses Dennison, Rachel L. Spreng, Matthew Reichartz, Sarah V. Mudrak, Fernando Ulloa-Montoya, Georgia D. Tomaras, Michelle Rojas, Scott Gregory, Ulrike Wille-Reece, Margherita Coccia, Kelly E. Seaton, Frederick Feely |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Malaria vaccine Immunology Neoplasms. Tumors. Oncology. Including cancer and carcinogens Plasmodium falciparum Biology RC581-607 medicine.disease biology.organism_classification Vaccine efficacy Subclass Article Malaria Circumsporozoite protein parasitic diseases medicine biology.protein Infectious diseases Pharmacology (medical) Avidity Antibody Immunologic diseases. Allergy RC254-282 |
| Zdroj: | NPJ Vaccines npj Vaccines, Vol 6, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2059-0105 |
| Popis: | RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum. |
| Databáze: | OpenAIRE |
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