Target antigens in malaria transmission blockling immunity

1984 ◽  
Vol 307 (1131) ◽  
pp. 201-213 ◽  
Keyword(s):  
Malaria Transmission ◽  
Subsequent Development ◽  
Mosquito Population ◽  
Malaria Parasites ◽  
Transmission Blocking ◽  
Mosquito Midgut ◽  
Single Protein ◽  
Phases Of Development ◽  
Blocking Antibodies ◽  
Selection Of

Malaria transmission blocking immunity has been found to operate against two distinct phases of development of malaria parasites in the mosquito midgut: (i) against the extracellular gametes and newly fertilized zygotes shortly after ingestion by a mosquito of parasitized blood and (ii) against the zygotes during their subsequent development into ookinetes. Immunity is antibody-mediated and stage-specific. A set of three proteins, synthesized in the gametocytes, expressed on the surface of the gametes and newly fertilized zygotes and subsequently shed during later transformation of the zygotes, has been identified as the target antigens of anti-gamete fertilization blocking antibodies. A single protein, synthesized and expressed on the zygote surface during its development to ookinetes, has been identified as the target of antibodies which block the development of the fertilized parasites in the mosquito. Immunization of hum an populations against gamete or zygote antigens, while not directly protecting an immunized individual from inflection, would reduce the transfer of malaria within the population. Such immunity, in addition to reducing the overall rate of malaria transmission, would, if combined with a vaccine against the asexual (disease-causing) stages, reduce the chance of selection of parasites that are resistant to the asexual vaccine by preventing their entry into the mosquito population.

The Search for Novel Malaria Transmission-blocking Targets in the Mosquito Midgut

1998 ◽  
Vol 14 (12) ◽  
pp. 493-497 ◽  
Author(s):  
M. Shahabuddin ◽  
S. Cociancich ◽  
H. Zieler
Keyword(s):  
Malaria Transmission ◽  
Transmission Blocking ◽  
Mosquito Midgut

scholarly journals Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Gregory P. Howard ◽  
Nicole G. Bender ◽  
Prachi Khare ◽  
Borja López-Gutiérrez ◽  
Vincent Nyasembe ◽  
...  
Keyword(s):  
Lymph Node ◽  
Malaria Transmission ◽  
Delivery System ◽  
Specific Antibody ◽  
High Antibody ◽  
Transmission Blocking ◽  
Mosquito Midgut ◽  
Cpg Oligodeoxynucleotide ◽  
Biodegradable Nanoparticle ◽  
Lymph Node Targeting

A successful malaria transmission blocking vaccine (TBV) requires the induction of a high antibody titer that leads to abrogation of parasite traversal of the mosquito midgut following ingestion of an infectious bloodmeal, thereby blocking the cascade of secondary human infections. Previously, we developed an optimized construct UF6b that elicits an antigen-specific antibody response to a neutralizing epitope of Anopheline alanyl aminopeptidase N (AnAPN1), an evolutionarily conserved pan-malaria mosquito midgut-based TBV target, as well as established a size-controlled lymph node targeting biodegradable nanoparticle delivery system that leads to efficient and durable antigen-specific antibody responses using the model antigen ovalbumin. Herein, we demonstrate that co-delivery of UF6b with the adjuvant CpG oligodeoxynucleotide immunostimulatory sequence (ODN ISS) 1018 using this biodegradable nanoparticle vaccine delivery system generates an AnAPN1-specific immune response that blocks parasite transmission in a standard membrane feeding assay. Importantly, this platform allows for antigen dose-sparing, wherein lower antigen payloads elicit higher-quality antibodies, therefore less antigen-specific IgG is needed for potent transmission-reducing activity. By targeting lymph nodes directly, the resulting immunopotentiation of AnAPN1 suggests that the de facto assumption that high antibody titers are needed for a TBV to be successful needs to be re-examined. This nanovaccine formulation is stable at -20°C storage for at least 3 months, an important consideration for vaccine transport and distribution in regions with poor healthcare infrastructure. Together, these data support further development of this nanovaccine platform for malaria TBVs.

Peptide mimics as surrogate immunogens of mosquito midgut carbohydrate malaria transmission blocking targets

Vaccine ◽  
2005 ◽  
Vol 23 (21) ◽  
pp. 2717-2724 ◽  
Author(s):  
Rhoel R. Dinglasan ◽  
Johanna M. Porter-Kelley ◽  
Uzma Alam ◽  
Abdu F. Azad
Keyword(s):  
Malaria Transmission ◽  
Peptide Mimics ◽  
Transmission Blocking ◽  
Mosquito Midgut

scholarly journals Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies.

1989 ◽  
Vol 169 (1) ◽  
pp. 135-147 ◽  
Author(s):  
R Carter ◽  
P M Graves ◽  
I A Quakyi ◽  
M F Good
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Antibody Response ◽  
Malaria Transmission ◽  
Surface Antigens ◽  
Surface Proteins ◽  
Human Populations ◽  
Sexual Stage ◽  
Transmission Blocking ◽  
Blocking Antibodies

We have studied the antibodies to sexual stage antigens of Plasmodium falciparum in human sera from Papua New Guinea where intense transmission of P. falciparum occurs as well as the less prevalent P. malariae and P. vivax. In extracts of gametes of P. falciparum we have studied the reactivity of serum antibodies with antigens labeled with 125I on the surface of the gametes as well as intracellular gamete antigens. A prominent 27-kD sexual stage-specific intracellular protein was recognized more or less in proportion to the general antibody response to gamete proteins. The response to the gamete surface proteins, however, was quite unrepresentative of the general antibody response to the intracellular gamete proteins. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of malaria transmission-blocking antibodies. The antibody response to two other target antigens of transmission-blocking antibodies on the surface of gametes of P. falciparum, a 230- and a 48- and 45-kD protein doublet, was very variable and independent of the response to the internal protein antigens. Several possibilities are discussed that may account for the variable response to these gamete surface antigens in individuals with otherwise good antibody responses to internal sexual stage proteins. Among these is the possibility that there is MHC restriction of the immune response to the gamete surface antigens in the human population. This interpretation accords well with evidence for MHC-restricted immune response to the same P. falciparum gamete surface antigens in studies with H-2 congenic mice (24).

scholarly journals Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yacob Keleta ◽  
Julian Ramelow ◽  
Liwang Cui ◽  
Jun Li
Keyword(s):  
Malaria Transmission ◽  
Molecular Interactions ◽  
Molecular Mechanisms ◽  
Considerable Effort ◽  
Transmission Blocking ◽  
Public Health Burden ◽  
Mosquito Midgut ◽  
Malaria Vaccines ◽  
Effective Transmission ◽  
Transmission Blocking Vaccines

AbstractDespite considerable effort, malaria remains a major public health burden. Malaria is caused by five Plasmodium species and is transmitted to humans via the female Anopheles mosquito. The development of malaria vaccines against the liver and blood stages has been challenging. Therefore, malaria elimination strategies advocate integrated measures, including transmission-blocking approaches. Designing an effective transmission-blocking strategy relies on a sophisticated understanding of the molecular mechanisms governing the interactions between the mosquito midgut molecules and the malaria parasite. Here we review recent advances in the biology of malaria transmission, focusing on molecular interactions between Plasmodium and Anopheles mosquito midgut proteins. We provide an overview of parasite and mosquito proteins that are either targets for drugs currently in clinical trials or candidates of promising transmission-blocking vaccines.

scholarly journals A Malaria Transmission-Blocking (+)-Usnic Acid Derivative PreventsPlasmodiumZygote-to-Ookinete Maturation in the Mosquito Midgut

2016 ◽  
Vol 11 (12) ◽  
pp. 3461-3472 ◽  
Author(s):  
Rebecca Pastrana-Mena ◽  
Derrick K. Mathias ◽  
Michael Delves ◽  
Krithika Rajaram ◽  
Jonas G. King ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Acid Derivative ◽  
Usnic Acid ◽  
Transmission Blocking ◽  
Mosquito Midgut

scholarly journals Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alyssa L. Kennedy ◽  
Kasiani C. Myers ◽  
James Bowman ◽  
Christopher J. Gibson ◽  
Nicholas D. Camarda ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Bone Marrow Failure ◽  
Subsequent Development ◽  
Genetic Constraints ◽  
Clonal Hematopoiesis ◽  
Clinical Surveillance ◽  
Clinical Consequences ◽  
Shwachman Diamond Syndrome ◽  
Mechanistic Basis ◽  
Selection Of

AbstractTo understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.

scholarly journals A Plant-Produced Pfs25 VLP Malaria Vaccine Candidate Induces Persistent Transmission Blocking Antibodies against Plasmodium falciparum in Immunized Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e79538 ◽  
Author(s):  
R. Mark Jones ◽  
Jessica A. Chichester ◽  
Vadim Mett ◽  
Jennifer Jaje ◽  
Stephen Tottey ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Vaccine Candidate ◽  
Transmission Blocking ◽  
Malaria Vaccine Candidate ◽  
Blocking Antibodies
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