scholarly journals Kinetics of Humoral and Memory B Cell Response Induced by the Plasmodium falciparum 19-Kilodalton Merozoite Surface Protein 1 in Mice

2011 ◽  
Vol 80 (2) ◽  
pp. 633-642 ◽  
Author(s):  
Mwanaidi Y. Kafuye-Mlwilo ◽  
Paushali Mukherjee ◽  
Virander S. Chauhan

ABSTRACTThe 19-kDa carboxyl-terminal fragment of the merozoite surface protein-1 (MSP-119) has been shown to regulate antibody (Ab)-mediated protective immunity to blood-stage malaria infection. But the serological memory to this antigen tends to be short-lived, and little is known of the mechanisms that regulate the formation of B cell memory to MSP-119antigen. We studied the formation of B cell memory response after immunization with the recombinant 19-kDaPlasmodium falciparummerozoite surface protein 1 (PfMSP-119). Immunization with PfMSP-119resulted in delayed increase in germinal center (GC) B cell numbers. This poor GC reaction correlated with short-lived PfMSP-119-specific antibodies in serum and the short life of PfMSP-119-specific plasma cells and memory B cells (MBCs) in spleen and bone marrow. PfMSP-119-specific MBCs were capable of producing antigen (Ag)-specific Ab-secreting cell (ASC) responses that were short-lived following challenge immunization of the immune mice with antigen or transgenicPlasmodium bergheiparasite expressing PfMSP-119in place of nativeP. bergheiMSP-119at 8 weeks after the last immunization or following adoptive transfer into naive hosts. However, no protection was achieved in PfMSP-119immune mice or recipient mice with PfMSP-119-specific MBCs following challenge with transgenicP. berghei. Our findings suggest that PfMSP-119-specific IgG production by short-lived plasma cells combined with the poor ability of the PfMSP-119-induced MBCs to maintain the anamnestic IgG responses failed to contribute to protection against infection.

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24852 ◽  
Author(s):  
Kiprotich Chelimo ◽  
Paula B. Embury ◽  
Peter Odada Sumba ◽  
John Vulule ◽  
Ayub V. Ofulla ◽  
...  

2002 ◽  
Vol 70 (6) ◽  
pp. 2772-2779 ◽  
Author(s):  
Alan L. Y. Pang ◽  
Caryn N. Hashimoto ◽  
Leslie Q. Tam ◽  
Z. Q. Meng ◽  
George S. N. Hui ◽  
...  

ABSTRACT The 42-kDa carboxyl-terminal processing fragment of Plasmodium falciparum merozoite surface protein 1 (MSP-142) is an anti-erythrocytic stage malaria vaccine candidate. In this study, MSP-142 was expressed by using the Bombyx mori nuclear polyhedrosis virus-silkworm expression system, and the antigenicity and immmunogenicity of the recombinant protein, Bmp42, were evaluated. The average yield of Bmp42, as determined by a sandwich enzyme-linked immunosorbent assay (ELISA), was 379 μg/ml of infected silkworm hemolymph, which was >100-fold higher than the level attainable in cell culture medium. N-terminal amino acid sequencing revealed that Bmp42 was correctly processed in silkworm cells. Data from immunoblotting, as well as from the inhibition ELISA, suggested that the conformational B-cell epitopes of MSP-142 were recreated in Bmp42. Immunization of rabbits with Bmp42 in complete Freund's adjuvant generated high-titer antibody responses against the immunogen. Specificity analyses of the anti-Bmp42 antibodies using several recombinant MSP-119 proteins expressing variant and conserved B-cell epitopes suggested that the anti-Bmp42 antibodies recognized primarily conserved epitopes on MSP-119. Furthermore, the anti-Bmp42 antibodies were highly effective in inhibiting the in vitro growth of parasites carrying homologous or heterologous MSP-142. Our results demonstrated that the baculovirus-silkworm expression system could be employed to express biologically and immunologically active recombinant MSP-142 at elevated levels; thus, it is an attractive alternative for producing a protective MSP-142 vaccine for human use.


2005 ◽  
Vol 73 (9) ◽  
pp. 5928-5935 ◽  
Author(s):  
Kevin K. A. Tetteh ◽  
David R. Cavanagh ◽  
Patrick Corran ◽  
Rosemary Musonda ◽  
Jana S. McBride ◽  
...  

ABSTRACT Polymorphism in pathogen antigens presents a complex challenge for vaccine design. A prime example is the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP1), to which allele-specific antibodies have been associated with protection from malaria. In a Zambian population studied here, 49 of 91 alleles sampled were of the K1-like type (the most common of three block 2 types in all African populations), and most of these had unique sequences due to variation in tri- and hexapeptide repetitive motifs. There were significant negative correlations between allelic sequence lengths of different regions of the repeats, so the complete repeat sequence had less length variation than its component parts, suggesting a constraint on overall length. Diverse epitopes recognized by three murine monoclonal antibodies and 24 individual human sera were then mapped by using a comprehensive panel of synthetic peptides, revealing epitopes in all regions of the repeats. To incorporate these different epitopes in a single molecule, a composite sequence of minimal overall length (78 amino acids) was then designed and expressed as a recombinant antigen. More human immune sera reacted with this “K1-like Super Repeat” antigen than with proteins consisting of single natural allelic sequences, and immunization of mice elicited antibodies that recognized a range of five cultured parasite lines with diverse K1-like MSP1 block 2 repeat sequences. Thus, complex allelic polymorphism was deconstructed and a minimal composite polyvalent antigen was engineered, delivering a designed candidate sequence for inclusion in a malaria vaccine.


Gene ◽  
2000 ◽  
Vol 241 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Kazuyuki Tanabe ◽  
Naoko Sakihama ◽  
Yoshimitu Nakamura ◽  
Osamu Kaneko ◽  
Masatugu Kimura ◽  
...  

2018 ◽  
Vol 14 (4) ◽  
pp. 106-109
Author(s):  
Rosye Hefmi Rechnelty Tanjung ◽  
Yulius Sarungu ◽  
Meidy Johana Imbiri ◽  
Ade Irma Resmol ◽  
Dirk Yanes Persius Runtuboi ◽  
...  

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