Stage-specific processing of Pfs230, a Plasmodium falciparum transmission-blocking vaccine candidate

A vaccine to prevent the transmission of malaria parasites from infected humans to mosquitoes is an important component for the elimination of malaria in the 21st century, yet it remains neglected as a priority of malaria vaccine development. The lead candidate forPlasmodium falciparumtransmission-blocking vaccine development, Pfs25, is a sexual stage surface protein that has been produced for vaccine testing in a variety of heterologous expression systems. Any realistic malaria vaccine will need to optimize proper folding balanced against cost of production, yield, and potentially reactogenic contaminants. HereChlamydomonas reinhardtiimicroalga-produced recombinant Pfs25 protein was formulated with four different human-compatible adjuvants (alum, Toll-like receptor 4 [TLR-4] agonist glucopyranosal lipid A [GLA] plus alum, squalene–oil-in-water emulsion, and GLA plus squalene–oil-in-water emulsion) and compared for their ability to induce malaria transmission-blocking antibodies. Alga-produced recombinant Pfs25 plus GLA plus squalene–oil-in-water adjuvant induced the highest titer and avidity in IgG antibodies, measured using alga-produced recombinant Pfs25 as the enzyme-linked immunosorbent assay (ELISA) antigen. These antibodies specifically reacted with the surface ofP. falciparummacrogametes and zygotes and effectively prevented parasites from developing within the mosquito vector in standard membrane feeding assays. Alga-produced Pfs25 in combination with a human-compatible adjuvant composed of a TLR-4 agonist in a squalene–oil-in-water emulsion is an attractive new vaccine candidate that merits head-to-head comparison with other modalities of vaccine production and administration.

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Transmission-blocking effects of sera from malaria-exposed individuals on Plasmodium falciparum isolates from gametocyte carriers

Parasitology ◽

10.1017/s0031182098002601 ◽

1998 ◽

Vol 116 (5) ◽

pp. 417-423 ◽

Cited By ~ 22

Author(s):

C. J. DRAKELEY ◽

L. MULDER ◽

T. TCHUINKAM ◽

S. GUPTA ◽

R. SAUERWEIN ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Vaccine Candidate ◽

Blocking Effect ◽

Transmission Blocking ◽

Positive Antibody ◽

Blocking Effects ◽

Vaccine Candidate Antigen ◽

And Control ◽

Transmission Blocking Vaccine ◽

Candidate Antigen

Sera from donors exposed to malaria were tested for their ability to block the transmission of isolates from Cameroonian Plasmodium falciparum gametocyte carriers. Sera were selected from amongst Cameroonian and Gambian donors who had positive antibody reactivity against the surface of activated gametes and against epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate antigen). Aliquots of washed blood from gametocyte carriers were resuspended in test and control sera and fed to An. gambiae mosquitoes via a membrane feeder. Comparisons of the prevalence and intensity of infections in dissected mosquitoes showed variations in the ability of sera to block the transmission of the different isolates. Sera were identified that had little or no blocking effect on the transmission of isolates unless the isolate was poorly infectious. Some sera completely blocked the transmission of some isolates whilst having little or no effect on others. The observed variation in transmission-modulating activity may have implications for the development of a transmission-blocking vaccine.

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Minimal variation in the transmission-blocking vaccine candidate Pfs4845 of the human malaria parasite Plasmodium falciparum

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(94)00193-q ◽

1995 ◽

Vol 69 (1) ◽

pp. 115-118 ◽

Cited By ~ 20

Author(s):

Clemens H.M. Kocken ◽

Richard L.B. Milek ◽

Ton H.W. Lensen ◽

David C. Kaslow ◽

John G.G. Schoenmakers ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Parasite ◽

Vaccine Candidate ◽

Human Malaria Parasite ◽

Transmission Blocking ◽

Human Malaria ◽

Parasite Plasmodium ◽

Parasite Plasmodium Falciparum ◽

Transmission Blocking Vaccine

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

Infection and Immunity ◽

10.1128/iai.73.11.7375-7380.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7375-7380 ◽

Cited By ~ 49

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.

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