The Use of Synthetic Carriers in Malaria Vaccine Design

Powles, Liam Michael; Xiang, Sue D.; Selomulya, Cordelia

doi:10.3390/vaccines3040894

Cited by 24 publications

(21 citation statements)

References 213 publications

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“…Inflammation is one of the common side effects associated with the use of most vaccine adjuvants (30). For example, the commonly licensed adjuvant alum specifically activates the NLRP3 inflammasome, whereas other adjuvants in more restricted use, such as MPLA in Cervarix, activate inflammation via the TLR4 receptor.…”

Section: Discussionmentioning

confidence: 99%

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

et al. 2020

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To be optimally effective, peptide-based vaccines need to be administered with adjuvants. Many currently available adjuvants are toxic, not biodegradable; they invariably invoke adverse reactions, including allergic responses and excessive inflammation. A nontoxic, biodegradable, biocompatible, self-adjuvanting vaccine delivery system is urgently needed. Herein, we report a potent vaccine delivery system fulfilling the above requirements. A peptide antigen was coupled with poly-hydrophobic amino acid sequences serving as self-adjuvanting moieties using solid-phase synthesis, to produce fully defined single molecular entities. Under aqueous conditions, these molecules self-assembled into distinct nanoparticles and chain-like aggregates. Following subcutaneous immunization in mice, these particles successfully induced opsonic epitope-specific antibodies without the need of external adjuvant. Mice immunized with entities bearing 15 leucine residues were able to clear bacterial load from target organs without triggering the release of soluble inflammatory mediators. Thus, we have developed a well-defined and effective self-adjuvanting delivery system for peptide antigens.

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Section: Discussionmentioning

confidence: 99%

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

et al. 2020

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“…Different strategies have been proposed for enhancing short peptides’ immunogenicity (i.e., natural or synthetic adjuvants or delivery system), such as using carriers [ 137 , 138 , 139 , 140 ], conjugation with T-helper and B-cell activation proteins [ 139 ], identifying cryptic epitopes [ 141 ], peptides mimicking native structures (Cys–Cys bond inclusion) [ 142 ], peptide elongation [ 143 ] and using MHCII peptide binding prediction servers for predicting new epitopes [ 144 ]. Most of the above approaches involve modifying peptide or epitope sequences so that MHC molecule and/or peptide-MHC complex binding affinity for TCR molecules becomes increased [ 145 ].…”

Section: Breaking the Parasite’s Immunological Code Of Silencementioning

confidence: 99%

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

et al. 2017

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Synthetic peptides have become invaluable biomedical research and medicinal chemistry tools for studying functional roles, i.e., binding or proteolytic activity, naturally-occurring regions’ immunogenicity in proteins and developing therapeutic agents and vaccines. Synthetic peptides can mimic protein sites; their structure and function can be easily modulated by specific amino acid replacement. They have major advantages, i.e., they are cheap, easily-produced and chemically stable, lack infectious and secondary adverse reactions and can induce immune responses via T- and B-cell epitopes. Our group has previously shown that using synthetic peptides and adopting a functional approach has led to identifying Plasmodium falciparum conserved regions binding to host cells. Conserved high activity binding peptides’ (cHABPs) physicochemical, structural and immunological characteristics have been taken into account for properly modifying and converting them into highly immunogenic, protection-inducing peptides (mHABPs) in the experimental Aotus monkey model. This article describes stereo–electron and topochemical characteristics regarding major histocompatibility complex (MHC)-mHABP-T-cell receptor (TCR) complex formation. Some mHABPs in this complex inducing long-lasting, protective immunity have been named immune protection-inducing protein structures (IMPIPS), forming the subunit components in chemically synthesized vaccines. This manuscript summarizes this particular field and adds our recent findings concerning intramolecular interactions (H-bonds or π-interactions) enabling proper IMPIPS structure as well as the peripheral flanking residues (PFR) to stabilize the MHCII-IMPIPS-TCR interaction, aimed at inducing long-lasting, protective immunological memory.

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“…However, further studies are required to expedite understanding of how changes in nanoparticle properties might affect an immunological response against malaria and thus contribute towards effective vaccine design [153].…”

Section: Future Directionsmentioning

confidence: 99%

Plasmodium falciparum pre-erythrocytic stage vaccine development

Molina-Franky

Cuy-Chaparro

Camargo

et al. 2020

Malar J

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Worldwide strategies between 2010 and 2017 aimed at controlling malarial parasites (mainly Plasmodium falciparum) led to a reduction of just 18% regarding disease incidence rates. Many biologically-derived anti-malarial vaccine candidates have been developed to date; this has involved using many experimental animals, an immense amount of work and the investment of millions of dollars. This review provides an overview of the current state and the main results of clinical trials for sporozoite-targeting vaccines (i.e. the parasite stage infecting the liver) carried out by research groups in areas having variable malaria transmission rates. However, none has led to promising results regarding the effective control of the disease, thereby making it necessary to complement such efforts at finding/introducing new vaccine candidates by adopting a multi-epitope, multi-stage approach, based on minimal subunits of the main sporozoite proteins involved in the invasion of the liver.

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The Use of Synthetic Carriers in Malaria Vaccine Design

Cited by 24 publications

References 213 publications

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines

Conserved Binding Regions Provide the Clue for Peptide-Based Vaccine Development: A Chemical Perspective

Plasmodium falciparum pre-erythrocytic stage vaccine development

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