Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria ParasitePlasmodium falciparum

Abstract

The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.

A Novel Antibody-Dependent Cellular Cytotoxicity Mechanism Involved in Defense against Malaria Requires Costimulation of Monocytes FcγRII and FcγRIII

“…A biological effect was detected at concentrations as low as 700 pM (100 ng/ml), i.e., at concentrations within the range at which hormones, including dopamine, cortisone, and testosterone, are effective (53). These concentrations are 1000-fold lower than those reported to achieve a 50% inhibition of merozoites invasion by Abs (54,55). The number of Ab molecules required to neutralize all antigenic targets in an invasion inhibition mechanism is understandably far larger than that required to trigger MN activation through Fc␥Rs.…”

Merozoite surface protein 1 recognition of host glycophorin A mediates malaria parasite invasion of red blood cells

“…33 In a separate study, antibodies against the MSP1 83 domain potently inhibited malaria invasion and growth relative to other domains of MSP1. 34 Similarly, another study tested the activity of purified erythrocyte glycophorins and demonstrated a significant inhibitory effect on parasite invasion. 35 Enzyme treatment of RBCs prior to glycophorin purification altered invasion inhibitory activity of purified glycophorins.…”

Genetic diversity in merozoite surface protein-1 and 2 amongPlasmodium falciparumisolates from malarious districts of tribal dominant state of Jharkhand, India

“…MSP-1 of P. falciparum is a major surface protein, with an approximate molecular size of 190 kDa that plays an important role in erythrocyte invasion by the merozoite (Holder and Blackman, 1994). The protein is a principal target of human immune responses (Ferreira et al, 2003;Woehlbier et al, 2006), and is a promising candidate for a blood stage subunit vaccine (Ferreira et al, 2003;Woehlbier et al, 2006). The MSP-1 gene has seven variable blocks that are separated either by conserved or semiconserved regions.…”