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Pf 155, a candidate for a blood stage vaccine in Plasmodium falciparum malaria
Abstract:
Pf 155 is a Mr 155,000 P. falciparum antigen, which is deposited in the erythrocyte membrane at merozoite invasion. The antigen is detected by a modified immunofluorescence assay giving staining of the surface of ring stage infected erythrocytes. Cell lines producing human monoclonal antibodies to Pf 155 were established and two different antibodies of IgM and IgG class, respectively, were characterized further. Both antibodies gave a strong surface immunofluorescence and in immunoblotting they react strongly with Pf 155, but also with some lower molecular weight material, including polypeptides of Mr 135,000 and 120,000. Both antibodies were efficient inhibitors of P. falciparum reinvasion in vitro. Pf 155 as well as the Mr 135,000 and 120,000 polypeptides were shown to bind with high affinity to human erythrocyte glycophorin. An octapeptide (GluGluAsnValGluHisAspAla) corresponding to a repeated sequence in Pf 155 was synthesized. Rabbit antibodies to the octapeptide gave a distinct surface immunofluorescence and reacted with Pf 155 and the Mr 135,000 and 120,000 polypeptides in immunoblotting. Human antibodies reacting with the octapeptide were isolated by affinity chromatography from the serum of a P. falciparum immune individual. These antibodies showed a strong reaction with Pf 155 as determined by immunoblotting and surface immunofluorescence. Pf 155 reactive antibodies affinity purified on monolayers of P. falciparum infected erythrocytes are very efficient inhibitors of parasite reinvasion. Such antibody preparations depleted of octapeptide reactive antibodies showed a markedly decreased reinvasion inhibitory capacity, while a high inhibitory activity was recovered in the octapeptide reactive antibodies. Pf 155 fulfills several criteria thought to be proper for antigens involved in anti-malarial protective immunity.
Insights
The Plasmodium falciparum 155 (Pf 155) antigen, crucial for merozoite invasion, shows potential for malaria vaccines. Antibodies targeting Pf 155 and its related polypeptides effectively inhibit parasite reinvasion.
Area of Science:
- Malariology
- Immunology
- Molecular Biology
Background:
- Pf 155 is a Plasmodium falciparum antigen found on the erythrocyte membrane during merozoite invasion.
- It is detected on the surface of ring-stage infected erythrocytes using immunofluorescence assays.
Purpose of the Study:
- To characterize human monoclonal antibodies against the Pf 155 antigen.
- To investigate the role of Pf 155 and its related polypeptides in parasite invasion and inhibition.
Main Methods:
- Establishment and characterization of human monoclonal antibodies (IgM and IgG) against Pf 155.
- Immunoblotting and immunofluorescence assays to detect antigen-antibody reactions.
- In vitro inhibition assays for Plasmodium falciparum reinvasion.
- Binding affinity studies with human erythrocyte glycophorin.
- Synthesis of an octapeptide from Pf 155 and generation of specific antibodies.
Main Results:
- Human monoclonal antibodies recognized Pf 155 and lower molecular weight polypeptides (Mr 135,000 and 120,000).
- Both antibody classes efficiently inhibited P. falciparum reinvasion in vitro.
- Pf 155 and related polypeptides bind with high affinity to erythrocyte glycophorin.
- Antibodies to a synthesized octapeptide from Pf 155 also showed inhibitory activity.
Conclusions:
- Pf 155 and its related polypeptides are implicated in erythrocyte invasion by P. falciparum.
- The octapeptide sequence is immunogenic and contributes to the inhibitory capacity of antibodies.
- Pf 155 exhibits characteristics of an antigen involved in protective immunity against malaria.