Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity

The circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, w...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2021-12, Vol.12, p.775659-775659
Main Authors: Kurtovic, Liriye, Drew, Damien R, Dent, Arlene E, Kazura, James W, Beeson, James G
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Animals
Antibodies, Protozoan - immunology
antibody
Antibody Specificity
circumsporozoite protein (CSP)
complement
Complement Fixation Tests
Humans
Immunology
malaria
Malaria - immunology
Malaria Vaccines - immunology
Middle Aged
Plasmodium falcifarum
Protozoan Proteins - immunology
Rabbits
Vaccination
vaccines
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.775659