MODULATION OF PLASMODIUM FALCIPARUM CIRCUMSPOROZOITE PROTEIN GENE EXPRESSION BY ANTIBODIES

C Cassandra

Authors

C Cassandra

Center for Malaria and Other Tropical Diseases, UEI Malaria, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua da Junqueira, 96, 1349-008 Lisbon, Portugal

Keywords

Plasmodium falciparum gene expression antibodies

Abstract

The Plasmodium falciparum circumsporozoite protein (CSP) is a crucial antigen expressed during the sporozoite stage of the malaria parasite’s lifecycle and is a key target for vaccine development. This study investigates the modulation of CSP gene expression by antibodies. We examined how specific antibodies influence CSP gene transcription and translation using in vitro assays with P. falciparum sporozoites and a recombinant CSP expression system. Our findings reveal that antibodies can significantly alter CSP gene expression, both upregulating and downregulating its production depending on their specificity and concentration. This modulation suggests that antibody-mediated immune responses could impact the efficacy of CSP-based vaccines and the overall immune response to malaria infection. These results provide insights into the potential mechanisms through which antibodies affect parasite antigen expression and highlight considerations for designing effective malaria vaccines.

Downloads

Download data is not yet available.

References

1

Fujinami RS, Oldstone MB. Alterations in expression of measles virus polypeptides by antibody: molecular events in antibody-induced antigenic modulation. J Immunol 1980; 125: 78-85.

2

Yuzawa Y, Brentjens J R, Brett J, et al. Antibody-mediated redistribution and shedding of endothelial antigens in the rabbit. J Immunol 1993; 150: 5633-5646.

3

Vaughan JA, Do Rosario V, Leland P, et al. Plasmodium falciparum; ingested anti-sporozoite antibodies affect sporogony in Anopheles stephensi mosquitoes. Exp Parasitol 1988; 66: 171-182.

4

Hollingdale MR, do Rosario V. Malaria transmission-enhancing activity in mosquitoes by mammalian host anti-sporozoite antibodies. Exp Parasitol 1989; 68: 365-368.

5

Peiris JS, Premawansa S, Ranawaka MB et al. Monoclonal and polyclonal antibodies both block and enhance transmission of human P vivax malaria. Am J Trop Med Hyg 1988; 39: 26-32.

6

Nudelman S, Renia L, Charoenvit Y, et al. Dual action of antisporozoite antibodies in vitro. J Immunol 1989; 143: 996-1000.

7

Shi YP, Udhayakumar V, Oloo AJ, et al. Differential effect and interaction of monocytes, hyperimmune sera, and immunoglobulin G on the growth of asexual stage Plasmodium falciparum parasites. Am J Trop Med Hyg 1999; 60: 135-141.

8

Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976; 193: 673-675.

9

Moormann AM, Hossler PA, Meshnick SR. Deferoxamine effects on Plasmodium falciparum gene expression. Mol Biochem Parasitol 1999; 98: 279-283

10

Alloueche A, Silveira H, Conway DJ, et al. High-throughput sequence typing of T-cell epitope polymorphisms in Plasmodium falciparum circumsporozoite protein. Mol Biochem Parasitol 2000; 106: 273-282.

11

Cohen S, McGregor IA, Carrington SC. Gamma-globulin and acquired immunity to human malaria. Nature 1961; 192: 733-777.

12

Cochrane AH, Uni S, Maracic M, et al. A circumsporozoite-like protein is present in micronemes of mature blood stages of malaria parasites. Exp Parasitol 1989; 69: 351-356.

13

Levitt A, Dimayuga FO, Ruvolo VR. Analysis of malarial transcripts using cDNA-directed polymerase chain reaction. J Parasitology 1993; 79: 653-662.

14

Ruvolo V, Altszuler R, Levitt A. The transcript encoding the circumsporozoite antigen of Plasmodium berghei utilizes heterogeneous polyadenylation sites. Mol Biochem Parasitol 1993; 57: 137-150.

15

Menard R, Sultan AA, Cortes C, et al. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 1997; 385: 336-340.