scholarly journals Effect of CpG Oligodeoxynucleotides on the Immunogenicity of Pfs25, a Plasmodium falciparum Transmission-Blocking Vaccine Antigen

2004 ◽  
Vol 72 (1) ◽  
pp. 584-588 ◽  
Author(s):  
Cevayir Coban ◽  
Ken J. Ishii ◽  
Anthony W. Stowers ◽  
David B. Keister ◽  
Dennis M. Klinman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Titer ◽  
Pathogen Transmission ◽  
Vaccine Antigen ◽  
Cpg Odn ◽  
Transmission Blocking ◽  
Cpg Oligodeoxynucleotides ◽  
Membrane Feeding ◽  
Antibody Levels ◽  
Transmission Blocking Vaccine

ABSTRACT Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (Al). Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-Al alone) and avidity. Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-Al alone, and the sera from the CpG ODN-coadministered group completely blocked the transmission of P. falciparum parasites to mosquitoes, as determined by membrane feeding assays. However, transmission-blocking experiments revealed that blocking efficacy was dependent on high-titer antibody levels, independent of isotypes. These results suggest that CpG ODN can be used as an adjuvant to enhance the immunogenicity of rPfs25 as a malaria transmission-blocking vaccine.

scholarly journals Elucidating functional epitopes within the N-terminal region of malaria transmission blocking vaccine antigen Pfs230

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Kazutoyo Miura ◽  
Eizo Takashima ◽  
Thao P. Pham ◽  
Bingbing Deng ◽  
Luwen Zhou ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Synthetic Peptide ◽  
Vaccine Antigen ◽  
Parasite Development ◽  
Transmission Blocking ◽  
Peptide Antigens ◽  
Membrane Feeding ◽  
Functional Antibodies ◽  
Enrichment Techniques ◽  
Transmission Blocking Vaccine

AbstractPfs230 is a leading malaria transmission blocking vaccine (TBV) candidate. Comprising 3135 amino acids (aa), the large size of Pfs230 necessitates the use of sub-fragments as vaccine immunogens. Therefore, determination of which regions induce functional antibody responses is essential. We previously reported that of 27 sub-fragments spanning the entire molecule, only five induced functional antibodies. A “functional” antibody is defined herein as one that inhibits Plasmodium falciparum parasite development in mosquitoes in a standard membrane-feeding assay (SMFA). These five sub-fragments were found within the aa 443–1274 range, and all contained aa 543–730. Here, we further pinpoint the location of epitopes within Pfs230 that are recognized by functional antibodies using antibody depletion and enrichment techniques. Functional epitopes were not found within the aa 918–1274 region. Within aa 443–917, further analysis showed the existence of functional epitopes not only within the aa 543–730 region but also outside of it. Affinity-purified antibodies using a synthetic peptide matching aa 543–588 showed activity in the SMFA. Immunization with a synthetic peptide comprising this segment, formulated either as a carrier-protein conjugate vaccine or with a liposomal vaccine adjuvant system, induced antibodies in mice that were functional in the SMFA. These findings provide key insights for Pfs230-based vaccine design and establish the feasibility for the use of synthetic peptide antigens for a malaria TBV.

scholarly journals Engineering a Virus-Like Particle as an Antigenic Platform for a Pfs47-Targeted Malaria Transmission-Blocking Vaccine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lampouguin Yenkoidiok-Douti ◽  
Adeline E. Williams ◽  
Gaspar E. Canepa ◽  
Alvaro Molina-Cruz ◽  
Carolina Barillas-Mury
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Malaria Transmission ◽  
Transmission Blocking ◽  
High Affinity ◽  
Virus Like Particle ◽  
Antibody Titers ◽  
Reducing Activity ◽  
Sexual Stages ◽  
Transmission Blocking Vaccine

AbstractWe recently characterized Pfs47, a protein expressed on the surface of sexual stages and ookinetes of Plasmodium falciparum, as a malaria transmission-blocking vaccine (TBV) target. Mice immunization induced antibodies that conferred strong transmission-reducing activity (TRA) at a concentration of 200 μg/mL. Here, we sought to optimize the Pfs47 vaccine to elicit higher titers of high-affinity antibodies, capable of inducing strong TRA at a lower concentration. We report the development and evaluation of a Pfs47-based virus-like particle (VLP) vaccine generated by conjugating our 58 amino acid Pfs47 antigen to Acinetobacter phage AP205-VLP using the SpyCatcher:SpyTag adaptor system. AP205-Pfs47 complexes (VLP-P47) formed particles of ~22 nm diameter that reacted with polyclonal anti-Pfs47 antibodies, indicating that the antigen was accessible on the surface of the particle. Mice immunized with VLP-P47 followed by a boost with Pfs47 monomer induced significantly higher antibody titers, with higher binding affinity to Pfs47, than mice that received two immunizations with either VLP-P47 (VLP-P47/VLP-P47) or the Pfs47 monomer (P47/P47). Purified IgG from VLP-P47/P47 mice had strong TRA (83–98%) at concentrations as low as 5 μg/mL. These results indicate that conjugating the Pfs47 antigen to AP205-VLP significantly enhanced antigenicity and confirm the potential of Pfs47 as a TBV candidate.

Plasmodium falciparum Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies

2021 ◽  
Vol 13 (597) ◽  
pp. eabg2112
Author(s):  
Abhai K. Tripathi ◽  
Miranda S. Oakley ◽  
Nitin Verma ◽  
Godfree Mlambo ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Phase 1 ◽  
Biological Properties ◽  
Natural Immunity ◽  
Specific Expression ◽  
Transmission Blocking ◽  
Male Development ◽  
Malaria Vaccines ◽  
Membrane Feeding ◽  
Vaccine Antigens

Malaria vaccines that disrupt the Plasmodium life cycle in mosquitoes and reduce parasite transmission in endemic areas are termed transmission-blocking vaccines (TBVs). Despite decades of research, there are only a few Plasmodium falciparum antigens that indisputably and reproducibly demonstrate transmission-blocking immunity. So far, only two TBV candidates have advanced to phase 1/2 clinical testing with limited success. By applying an unbiased transcriptomics-based approach, we have identified Pf77 and male development gene 1 (PfMDV-1) as two P. falciparum TBV antigens that, upon immunization, induced antibodies that caused reductions in oocyst counts in Anopheles mosquito midguts in a standard membrane feeding assay. In-depth studies were performed to characterize the genetic diversity of, stage-specific expression by, and natural immunity to these two molecules to evaluate their suitability as TBV candidates. Pf77 and PfMDV-1 display limited antigenic polymorphism, are pan-developmentally expressed within the parasite, and induce naturally occurring antibodies in Ghanaian adults, which raises the prospect of natural boosting of vaccine-induced immune response in endemic regions. Together, these biological properties suggest that Pf77 and PfMDV-1 may warrant further investigation as TBV candidates.

Geographical distribution of a variant epitope of Pfs4845, a Plasmodium falciparum transmission-blocking vaccine candidate

1996 ◽  
Vol 81 (2) ◽  
pp. 253-257 ◽  
Author(s):  
Christopher J Drakeley ◽  
Manoj T Duraisingh ◽  
Marinete Póvoa ◽  
David J Conway ◽  
Geoffrey A.T Targett ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Geographical Distribution ◽  
Vaccine Candidate ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccine

Plasmodium falciparum: Immunogenicity of Alum-Adsorbed Clinical-Grade TBV25–28, a Yeast-Secreted Malaria Transmission-Blocking Vaccine Candidate

2001 ◽  
Vol 97 (2) ◽  
pp. 61-69 ◽  
Author(s):  
Mary Margaret G Gozar ◽  
Olga Muratova ◽  
David B Keister ◽  
Charlotte R Kensil ◽  
Virginia L Price ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Vaccine Candidate ◽  
Clinical Grade ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccine

scholarly journals Monoclonal Antibody against the Plasmodium falciparum Chitinase, PfCHT1, Recognizes a Malaria Transmission-Blocking Epitope in Plasmodium gallinaceum Ookinetes Unrelated to the Chitinase PgCHT1

2002 ◽  
Vol 70 (3) ◽  
pp. 1581-1590 ◽  
Author(s):  
Rebecca C. Langer ◽  
Fengwu Li ◽  
Vsevolod Popov ◽  
Alexander Kurosky ◽  
Joseph M. Vinetz
Keyword(s):  
Monoclonal Antibody ◽  
Plasmodium Falciparum ◽  
Synthetic Peptide ◽  
Transmission Blocking ◽  
Reducing Conditions ◽  
Membrane Feeding ◽  
Epithelial Cell Surface ◽  
A Subunit ◽  
35 Kda Protein ◽  
Homologous Amino Acid

ABSTRACT To initiate invasion of the mosquito midgut, Plasmodium ookinetes secrete chitinases that are necessary to cross the chitin-containing peritrophic matrix en route to invading the epithelial cell surface. To investigate chitinases as potential immunological targets of blocking malaria parasite transmission to mosquitoes, a monoclonal antibody (MAb) was identified that neutralized the enzymatic activity of the sole chitinase of Plasmodium falciparum, PfCHT1, identified to date. This MAb, designated 1C3, previously shown to react with an apical structure of P. falciparum ookinetes, also reacts with a discrete apical structure of P. gallinaceum ookinetes. In membrane feeding assays, MAb 1C3 markedly inhibited P. gallinaceum oocyst development in mosquito midguts. MAb 1C3 affinity isolated an ∼210-kDa antigen which, under reducing conditions, became a 35-kDa antigen. This isolated 35-kDa protein cross-reacted with an antiserum raised against a synthetic peptide derived from the P. gallinaceum chitinase active site, PgCHT1, even though MAb 1C3 did not recognize native or recombinant PgCHT1 on Western blot. Therefore, this affinity-purified 35-kDa antigen appears similar to a previously identified protein, PgCHT2, a putative second chitinase of P. gallinaceum. Epitope mapping indicated MAb 1C3 recognized a region of PfCHT1 that diverges from a homologous amino acid sequence conserved within sequenced chitinases of P. berghei, P. yoelii, and P. gallinaceum (PgCHT1). A synthetic peptide derived from the mapped 1C3 epitope may be useful as a component of a subunit transmission-blocking vaccine.

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