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.