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Plasmodium riboprotein PfP0 induces a deviant humoral immune response in Balb/c mice
Sulabha Pathak1, K Rajeshwari, Swati Garg
1Malarial Parasite Biology Laboratory, Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India. suepathak@tifr.res.in
Abstract:
Passive immunization with antibodies to recombinant Plasmodium falciparum P0 riboprotein (rPfP0, 61-316 amino acids) provides protection against malaria. Carboxy-terminal 16 amino acids of the protein (PfP0C0) are conserved and show 69% identity to human and mouse P0. Antibodies to this domain are found in 10-15% of systemic lupus erythematosus patients. We probed the nature of humoral response to PfP0C0 by repeatedly immunizing mice with rPfP0. We failed to raise stable anti-PfP0C0 hybridomas from any of the 21 mice. The average serum anti-PfP0C0 titer remained low (5.1 ± 1.3 × 10⁴). Pathological changes were observed in the mice after seven boosts. Adsorption with dinitrophenyl hapten revealed that the anti-PfP0C0 response was largely polyreactive. This polyreactivity was distributed across all isotypes. Similar polyreactive responses to PfP0 and PfP0C0 were observed in sera from malaria patients. Our data suggests that PfP0 induces a deviant humoral response, and this may contribute to immune evasion mechanisms of the parasite.
Insights
Passive immunization with Plasmodium falciparum P0 riboprotein (PfP0) antibodies protects against malaria. However, the PfP0 protein induces a deviant, polyreactive humoral immune response, potentially aiding parasite immune evasion.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Recombinant Plasmodium falciparum P0 riboprotein (rPfP0) antibodies offer protection against malaria.
- The conserved carboxy-terminal domain (PfP0C0) shares identity with human and mouse P0, with antibodies found in some lupus erythematosus patients.
Purpose of the Study:
- To investigate the nature of the humoral immune response to the PfP0C0 domain.
- To understand the immune response to rPfP0 in mice and malaria patients.
Main Methods:
- Repeated immunization of mice with rPfP0.
- Analysis of serum antibody titers and hybridoma generation.
- Dinitrophenyl hapten adsorption to assess antibody polyreactivity.
- Examination of sera from malaria patients.
Main Results:
- Failure to generate stable anti-PfP0C0 hybridomas and low average serum titers.
- Observation of pathological changes in mice after repeated immunization.
- Demonstration of significant polyreactivity in the anti-PfP0C0 response across all isotypes.
- Detection of similar polyreactive responses in malaria patients' sera.
Conclusions:
- Plasmodium falciparum P0 riboprotein induces a deviant humoral immune response.
- This aberrant immune response may be a mechanism for parasite immune evasion.
