Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity

Scaria, Puthupparampil V.; Chen, Beth; Rowe, Christopher G.; Jones, David S.; Barnafo, Emma K.; Fischer, Elizabeth R.; Anderson, Charles; MacDonald, Nicholas J.; Lambert, Lynn; Rausch, Kelly M.; Narum, David L.; Duffy, Patrick E.

doi:10.1371/journal.pone.0190312

Cited by 40 publications

(46 citation statements)

References 62 publications

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“…The development of Pfs230D1 as a conjugate vaccine to form a nanoparticle 49 , has provided a significant step forward toward development of a malaria TB vaccine. If the result from the current Phase 2 trial of a Pfs230D1-EPA conjugated nanoparticle formulated in AS01 (clinicaltrials.gov ID NCT03917654) shows the vaccine to be insufficient, then a clear next step is further investment in the development of Pfs48/45 using a scalable process with good productivity and quality for inclusion of Pfs48/ 45 as an additional TB vaccine component.…”

Section: Discussionmentioning

confidence: 99%

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

et al. 2020

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Proteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.

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Section: Discussionmentioning

confidence: 99%

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

et al. 2020

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“…These adjuvants in conjugation with specific antigens ranging in size from 16 to 73 nm diameter upon injection into the mice showed a better immune response against malaria as compared with antigens alone. 62 However, the extrinsic protein adjuvants have a limited use due to their low compatibility with target vaccine/antigens. 63 More recently, Kaba et al 64 has developed and designed a self-assembling protein nanoparticles (SAPNs) containing epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) and portions of the tool-like receptor 5 (TLR5) agonist flagellin as an intrinsic adjuvant, which was more immunogenic and protective in the mouse model.…”

Section: Protein-based Nano-therapy For Malariamentioning

confidence: 99%

<p>Nano-biotechnology: a new approach to treat and prevent malaria</p>

Rahman¹,

Khan²,

Fahad³

et al. 2019

IJN

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Malaria, the exterminator of ~1.5 to 2.7 million human lives yearly, is a notorious disease known throughout the world. The eradication of this disease is difficult and a challenge to scientists. Vector elimination and effective chemotherapy for the patients are key tactics to be used in the fight against malaria. However, drug resistance and environmental and social concerns are the main hurdles in this fight against malaria. Overcoming these limitations is the major challenge for the 21st-century malarial researchers. Adapting the principles of nano-biotechnology to both vector control and patient therapy is the only solution to the problem. Several compounds such as lipids, proteins, nucleic acid and metallic nanoparticles (NPs) have been successfully used for the control of this lethal malaria disease. Other useful natural reagents such as microbes and their products, carbohydrates, vitamins, plant extracts and biodegradable polymers, are also used to control this disease. Among these particles, the plant-based particles such as leaf, root, stem, latex, and seed give the best antagonistic response against malaria. In the present review, we describe certain efforts related to the control, prevention and treatment of malaria. We hope that this review will open new doors for malarial research.

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“…The conjugate was 16-73 nm in size. These findings suggest that various carriers and appropriate chemistry can be used for protein-protein conjugation for effective vaccine development [54].…”

Section: Polymer-based Nanocarriersmentioning

confidence: 99%

Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity

Jain

Vishwakarma

Gautam

et al. 2020

Drug Deliv. and Transl. Res.

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Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery.

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Protein-protein conjugate nanoparticles for malaria antigen delivery and enhanced immunogenicity

Cited by 40 publications

References 62 publications

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

<p>Nano-biotechnology: a new approach to treat and prevent malaria</p>

Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity

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