Antibodies to malaria peptide mimics inhibit Plasmodium falciparum invasion of erythrocytes.

Abstract:

:Apical membrane antigen 1 (AMA1) is expressed on the surfaces of Plasmodium falciparum merozoites and is thought to play an important role in the invasion of erythrocytes by malaria parasites. To select for peptides that mimic conformational B-cell epitopes on AMA1, we screened a phage display library of >10(8) individual peptides for peptides bound by a monoclonal anti-AMA1 antibody, 4G2dc1, known to inhibit P. falciparum invasion of erythrocytes. The most reactive peptides, J1, J3, and J7, elicited antibody responses in rabbits that recognized the peptide immunogen and both recombinant and parasite AMA1. Human antibodies in plasma samples from individuals exposed to chronic malaria reacted with J1 and J7 peptides and were isolated using immobilized peptide immunoadsorbents. Both rabbit and human antibodies specific for J1 and J7 peptides were able to inhibit the invasion of erythrocytes by P. falciparum merozoites. This is the first example of phage-derived peptides that mimic an important epitope of a blood-stage malaria vaccine candidate, inducing and isolating functional protective antibodies. Our data support the use of J1 and J7 peptide mimics as in vitro correlates of protective immunity in future AMA1 vaccine trials.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Casey JL,Coley AM,Anders RF,Murphy VJ,Humberstone KS,Thomas AW,Foley M

doi

10.1128/iai.72.2.1126-1134.2004

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

1126-34

issue

2

eissn

0019-9567

issn

1098-5522

journal_volume

72

pub_type

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