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.

Malaria transmission-blocking vaccines: wheat germ cell-free technology can accelerate vaccine development

2019 ◽  
Vol 18 (10) ◽  
pp. 1017-1027
Author(s):  
Kazutoyo Miura ◽  
Mayumi Tachibana ◽  
Eizo Takashima ◽  
Masayuki Morita ◽  
Bernard N. Kanoi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Malaria Transmission ◽  
Wheat Germ ◽  
Vaccine Development ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines

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.

scholarly journals Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Puthupparampil V. Scaria ◽  
Charles Anderson ◽  
Olga Muratova ◽  
Nada Alani ◽  
Hung V. Trinh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Malaria Transmission ◽  
Functional Activity ◽  
Rhesus Macaques ◽  
Transmission Blocking ◽  
Tlr4 Agonist ◽  
Functional Immunity ◽  
Antibody Levels ◽  
Transmission Blocking Vaccines ◽  
Better Than

AbstractMalaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.

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 No evidence for positive selection at two potential targets for malaria transmission-blocking vaccines in Anopheles gambiae s.s

2013 ◽  
Vol 16 ◽  
pp. 87-92 ◽  
Author(s):  
Jacob E. Crawford ◽  
Susan M. Rottschaefer ◽  
Boubacar Coulibaly ◽  
Madjou Sacko ◽  
Oumou Niaré ◽  
...  
Keyword(s):  
Positive Selection ◽  
Anopheles Gambiae ◽  
Malaria Transmission ◽  
Anopheles Gambiae S.S ◽  
Transmission Blocking ◽  
Transmission Blocking Vaccines

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.

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