Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

Reyes, César; Rojas-Luna, Rocío; Aza-Conde, Jorge; Tabares, Luisa; Patarroyo, Manuel A.; Patarroyo, Manuel Elkín

doi:10.1016/j.bbrc.2017.05.123

Cited by 6 publications

(3 citation statements)

References 25 publications

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“…Our recent findings involving 1 H-NMR structural analysis and physico-chemical features regarding the effects of peripheral flanking residues on peptide-based malaria vaccine development [ 266 ] have demonstrated that −p2 (N-terminus) and p10 (C-Terminus) directly influence the immunological behavior of 20 mer-long peptides when used as vaccine candidates. MHCII’ F51α, A52α, S53α, F54α and V85β were the main contacts residues for the aa located in −p2, whilst MHCII’ A68α, N69α, I72α, D57β, W61β and L67β were the main aa contacting p10.…”

Section: Peripheral Flanking Residues (Pfr)mentioning

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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Section: Peripheral Flanking Residues (Pfr)mentioning

confidence: 99%

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

et al. 2017

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“…As previously stated (Reyes et al, 2017b ), we have been increasing the amount of molecules analyzed. Group A (LLPI-IMPIPS) had a clear preference in –p2 for amide residues Q (4/12) and N (2/12), sulfur-containing M (3/12) and short alcohol (T), aliphatic amino acids (L) or β-branched apolar (V) amino acids, one per group.…”

Section: Resultsmentioning

confidence: 84%

“…Vey recently we demonstrated N-terminal peripheral flanking residue (PFR) (Reyes et al, 2017b ) preference for amide (Q, N), sulfur-containing (M) and one having β-branched apolar (V) or large aliphatic (L) residues in IMPIPS position –p2. We have also shown preference for charged (E, K, R, D, H) and short polar (S, T) residues in SPI mHABP position –p2 (Reyes et al, 2017b ).…”

Section: Resultsmentioning

confidence: 98%

Specific β-Turns Precede PPIIL Structures Binding to Allele-Specific HLA-DRβ1* PBRs in Fully-Protective Malaria Vaccine Components

et al. 2018

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The 3D structural analysis of 62 peptides derived from highly pathogenic Plasmodium falciparum malaria parasite proteins involved in host cell invasion led to finding a striking association between particular β-turn types located in the N-terminal peripheral flanking residue region (preceding the polyproline II left-handed structures fitting into the HLA-DRβ* allele family) and modified immune protection-inducing protein structure induced long-lasting protective immunity. This is the first time association between two different secondary structures associated with a specific immunological function has been described: full, long-lasting protective immunity.

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Impact of high human genetic diversity in Africa on immunogenicity and efficacy of RTS,S/AS01 vaccine

et al. 2023

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In modern medicine, vaccination is one of the most effective public health strategies to prevent infectious diseases. Indisputably, vaccines have saved millions of lives by reducing the burden of many serious infections such as polio, tuberculosis, measles, pneumonia, and tetanus. Despite the recent recommendation by the World Health Organization (WHO) to roll out RTS,S/AS01, this malaria vaccine still faces major challenges of variability in its efficacy partly due to high genetic variation in humans and malaria parasites. Immune responses to malaria vary between individuals and populations. Human genetic variation in immune system genes is the probable cause for this heterogeneity. In this review, we will focus on human genetic factors that determine variable responses to vaccination and how variation in immune system genes affect the immunogenicity and efficacy of the RTS,S/AS01 vaccine.

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Critical role of HLA-DRβ* binding peptides' peripheral flanking residues in fully-protective malaria vaccine development

Cited by 6 publications

References 25 publications

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

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

Specific β-Turns Precede PPIIL Structures Binding to Allele-Specific HLA-DRβ1* PBRs in Fully-Protective Malaria Vaccine Components

Impact of high human genetic diversity in Africa on immunogenicity and efficacy of RTS,S/AS01 vaccine

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