scholarly journals Carboxypeptidases B of Anopheles gambiae as Targets for a Plasmodium falciparum Transmission-Blocking Vaccine

2007 ◽  
Vol 75 (4) ◽  
pp. 1635-1642 ◽  
Author(s):  
C. Lavazec ◽  
C. Boudin ◽  
R. Lacroix ◽  
S. Bonnet ◽  
A. Diop ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Reproductive Capacity ◽  
Parasite Development ◽  
Carboxypeptidase B ◽  
Human Malaria Parasite ◽  
Transmission Blocking ◽  
Mosquito Midgut ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT Anopheles gambiae is the major African vector of Plasmodium falciparum, the most deadly species of human malaria parasite and the most prevalent in Africa. Several strategies are being developed to limit the global impact of malaria via reducing transmission rates, among which are transmission-blocking vaccines (TBVs), which induce in the vertebrate host the production of antibodies that inhibit parasite development in the mosquito midgut. So far, the most promising components of a TBV are parasite-derived antigens, although targeting critical mosquito components might also successfully block development of the parasite in its vector. We previously identified A. gambiae genes whose expression was modified in P. falciparum-infected mosquitoes, including one midgut carboxypeptidase gene, cpbAg1. Here we show that P. falciparum up-regulates the expression of cpbAg1 and of a second midgut carboxypeptidase gene, cpbAg2, and that this up-regulation correlates with an increased carboxypeptidase B (CPB) activity at a time when parasites establish infection in the mosquito midgut. The addition of antibodies directed against CPBAg1 to a P. falciparum-containing blood meal inhibited CPB activity and blocked parasite development in the mosquito midgut. Furthermore, the development of the rodent parasite Plasmodium berghei was significantly reduced in mosquitoes fed on infected mice that had been immunized with recombinant CPBAg1. Lastly, mosquitoes fed on anti-CPBAg1 antibodies exhibited reduced reproductive capacity, a secondary effect of a CPB-based TBV that could likely contribute to reducing Plasmodium transmission. These results indicate that A. gambiae CPBs could constitute targets for a TBV that is based upon mosquito molecules.

A new Plasmodium falciparum field isolate from Benin in continuous culture: Infectivity of fresh-produced and cryopreserved gametocytes to Anopheles gambiae

2021 ◽  
Author(s):  
Adandé A. Medjigbodo ◽  
Festus K. Acquah ◽  
Laurette Djossou ◽  
Linda E. Amoah ◽  
Edgard-Marius Ouendo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Field Isolate ◽  
Infected Mosquito ◽  
Developmental Cycle ◽  
Transmission Blocking ◽  
Field Isolates ◽  
Replication Studies ◽  
Intraerythrocytic Developmental Cycle ◽  
Transmission Blocking Vaccines

Abstract Transmission-blocking vaccines and drugs are likely to be key interventions in efforts to achieve malaria elimination. However, transmission-blocking studies are reliant upon a limited number of culture-adapted strains of Plasmodium falciparum with limited genetic variability, or on field isolates which are only maintained transiently in the laboratory and therefore not amenable to replication studies. Herein, we investigated the gametocytogenesis capacity and infectivity to Anopheles gambiae mosquitoes of a P. falciparum field isolate collected from a malaria patient from Benin compared to those of NF54 strain. The intraerythrocytic developmental cycle (IDC) was similar in both P. falciparum strains (ranges of parasitaemias were respectively 0.02–11.53% and 0.035–10.5% throughout twelve days of culture). The culture-adapted parasites displayed a significant higher infectivity to An. gambiae compared to that of NF54 (mean oocyst prevalence and intensity: 16.94%, CI95%= [15.15–18.73] vs. 3.13%, CI95%= [2.30–3.96], p < 0.0001 and 3 vs. 1 oocysts/infected mosquito, p = 0.002 respectively). Even after cryopreservation for up to 14 days, gametocytes from the field isolates were capable of infecting An. gambiae mosquitoes at a prevalence of up to 30% with an average of 12 oocysts/ midgut. This new P. falciparum strain will enhance malaria transmission-blocking studies in endemic countries.

scholarly journals Transmission-Blocking Vaccines: Old Friends and New Prospects

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Festus K. Acquah ◽  
Joshua Adjah ◽  
Kim C. Williamson ◽  
Linda E. Amoah
Keyword(s):  
Clinical Trials ◽  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Surface Antigens ◽  
Transmission Blocking ◽  
Content Type ◽  
Transmission Cycle ◽  
Mosquito Midgut ◽  
Transmission Blocking Vaccines ◽  
Old Friends

ABSTRACTIn the progression of the life cycle ofPlasmodium falciparum, a small proportion of asexual parasites differentiate into male or female sexual forms called gametocytes. Just like their asexual counterparts, gametocytes are contained within the infected host’s erythrocytes (RBCs). However, unlike their asexual partners, they do not exit the RBC until they are taken up in a blood meal by a mosquito. In the mosquito midgut, they are stimulated to emerge from the RBC, undergo fertilization, and ultimately produce tens of thousands of sporozoites that are infectious to humans. This transmission cycle can be blocked by antibodies targeting proteins exposed on the parasite surface in the mosquito midgut, a process that has led to the development of candidate transmission-blocking vaccines (TBV), including some that are in clinical trials. Here we review the leading TBV antigens and highlight the ongoing search for additional gametocyte/gamete surface antigens, as well as antigens on the surfaces of gametocyte-infected erythrocytes, which can potentially become a new group of TBV candidates.

scholarly journals Murine Model for Assessment of Plasmodium falciparum Transmission-Blocking Vaccine Using Transgenic Plasmodium berghei Parasites Expressing the Target Antigen Pfs25

2008 ◽  
Vol 76 (5) ◽  
pp. 2018-2024 ◽  
Author(s):  
Godfree Mlambo ◽  
Jorge Maciel ◽  
Nirbhay Kumar
Keyword(s):  
Animal Model ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Plasmodium Berghei ◽  
Target Antigen ◽  
Wild Type ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT Currently, there is no animal model for Plasmodium falciparum challenge to evaluate malaria transmission-blocking vaccines based on the well-established Pfs25 target antigen. The biological activity of transmission-blocking antibodies is typically assessed using an assay known as the membrane feeding assay (MFA). It is an in vitro method that involves mixing antibodies with cultured P. falciparum gametocytes and feeding them to mosquitoes through an artificial membrane followed by assessment of infection in the mosquitoes. We genetically modified Plasmodium berghei to express Pfs25 and demonstrated that the transgenic parasites (TrPfs25Pb) are susceptible to anti-Pfs25 antibodies during mosquito-stage development. The asexual growth kinetics and mosquito infectivity of TrPfs25Pb were comparable to those of wild-type parasites, and TrPfs25Pb displayed Pfs25 on the surface of ookinetes. Immune sera from nonhuman primates immunized with a Pfs25-based vaccine when passively transferred to mice blocked transmission of TrPfs25Pb to Anopheles stephensi. Furthermore, mice immunized with Pfs25 DNA vaccine and challenged with TrPfs25Pb displayed reduced malaria transmission compared to mice immunized with wild-type plasmid. These studies describe development of an animal malaria model alternative to the in vitro MFA and show that the model can facilitate P. falciparum transmission-blocking vaccine evaluation based on the target antigen Pfs25. We believe that an animal model to test transmission-blocking vaccines would be superior to the MFA, since there may be additional immune factors that synergize the transmission-blocking activity of antibodies in vivo.

scholarly journals Nasal Immunization with a Malaria Transmission-Blocking Vaccine Candidate, Pfs25, Induces Complete Protective Immunity in Mice against Field Isolates of Plasmodium falciparum

2005 ◽  
Vol 73 (11) ◽  
pp. 7375-7380 ◽  
Author(s):  
Takeshi Arakawa ◽  
Ai Komesu ◽  
Hitoshi Otsuki ◽  
Jetsumon Sattabongkot ◽  
Rachanee Udomsangpetch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Vaccine Candidate ◽  
Expression Patterns ◽  
Serum Antibody ◽  
Biologically Active ◽  
Mucosal Transmission ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT Malaria transmission-blocking vaccines based on antigens expressed in sexual stages of the parasites are considered one promising strategy for malaria control. To investigate the feasibility of developing noninvasive mucosal transmission-blocking vaccines against Plasmodium falciparum, intranasal immunization experiments with Pichia pastoris-expressed recombinant Pfs25 proteins were conducted. Mice intranasally immunized with the Pfs25 proteins in the presence of a potent mucosal adjuvant cholera toxin induced robust systemic as well as mucosal antibodies. All mouse immunoglobulin G (IgG) subclasses except IgG3 were found in serum at comparable levels, suggesting that the immunization induced mixed Th1 and Th2 responses. Consistent with the expression patterns of the Pfs25 proteins in the parasites, the induced immune sera specifically recognized ookinetes but not gametocytes. In addition, the immune sera recognized Pfs25 proteins with the native conformation but not the denatured forms, indicating that mucosal immunization induced biologically active antibodies capable of recognizing conformational epitopes of native Pfs25 proteins. Feeding Anopheles dirus mosquitoes with a mixture of the mouse immune sera and gametocytemic blood derived from patients infected with P. falciparum resulted in complete interference with oocyst development in mosquito midguts. The observed transmission-blocking activities were strongly correlated with specific serum antibody titers. Our results demonstrated for the first time that a P. falciparum transmission-blocking vaccine candidate is effective against field-isolated parasites and may justify the investigation of noninvasive mucosal vaccination regimens for control of malaria, a prototypical mucosa-unrelated mosquito-borne parasitic disease.

scholarly journals Exploring the lower thermal limits for development of the human malaria parasite, Plasmodium falciparum

2019 ◽  
Vol 15 (6) ◽  
pp. 20190275 ◽  
Author(s):  
Jessica L. Waite ◽  
Eunho Suh ◽  
Penelope A. Lynch ◽  
Matthew B. Thomas
Keyword(s):  
Plasmodium Falciparum ◽  
Future Climate Change ◽  
Parasite Development ◽  
Temperature Dependent ◽  
Human Malaria Parasite ◽  
Thermal Limits ◽  
Degree Day ◽  
Extrinsic Incubation Period ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The rate of malaria transmission is strongly determined by parasite development time in the mosquito, known as the extrinsic incubation period (EIP), since the quicker parasites develop, the greater the chance that the vector will survive long enough for the parasite to complete development and be transmitted. EIP is known to be temperature-dependent but this relationship is surprisingly poorly characterized. There is a single degree-day model for EIP of Plasmodium falciparum that derives from a limited number of poorly controlled studies conducted almost a century ago. Here, we show that the established degree-day model greatly underestimates the rate of development of P. falciparum in both Anopheles stephensi and An. gambiae mosquitoes at temperatures in the range of 17–20°C. We also show that realistic daily temperature fluctuation further speeds parasite development. These novel results challenge one of the longest standing models in malaria biology and have potentially important implications for understanding the impacts of future climate change.

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.

Sign in / Sign up

Export Citation Format

Share Document