Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

Author:

Seaton Kelly E.ORCID,Spreng Rachel L.ORCID,Abraha Milite,Reichartz Matthew,Rojas Michelle,Feely Frederick,Huntwork Richard H. C.,Dutta Sheetij,Mudrak Sarah V.,Alam S. Munir,Gregory Scott,Jongert Erik,Coccia MargheritaORCID,Ulloa-Montoya Fernando,Wille-Reece Ulrike,Tomaras Georgia D.ORCID,Dennison S. MosesORCID

Abstract

AbstractRTS,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.

Funder

Bill and Melinda Gates Foundation

United States Department of Defense | United States Army | Army Medical Command | Walter Reed Army Institute of Research

PATH Malaria Vaccine Initiative

GlaxoSmithKline

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology

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