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IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

Patarroyo ME, Bermúdez A, Alba MP, Vanegas M, Moreno-Vranich A, Poloche LA, Patarroyo MA - PLoS ONE (2015)

Bottom Line: Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures.They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR).Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response.

View Article: PubMed Central - PubMed

Affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad Nacional de Colombia, Bogotá, Colombia.

ABSTRACT
Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.

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Related in: MedlinePlus

WB analysis showing the reactivity of Aotus immunised with different mixtures of mHABPs.A. Reactivity with CSP-derived 25608, 32958, and TRAP 24246 mHABP mixtures 140 days after first immunisation (80 days after 3rd or III80) showing reactivity in 2/8 Aotus with CSP-rI. B. Reactivity with CSP-derived 25608, 32958, and TRAP 24254 and 24246 mHABP mixtures evidencing reactivity with CSP-rII and with TRAP rII in 5/6 Aotus monkeys C. Reactivity with CSP-derived rI 25608, rII 32958, TRAP rII 24254, MSP-2 24112, EBA-175 RI 13790 and rII 24292 and AMA-1 10022.
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pone.0123249.g002: WB analysis showing the reactivity of Aotus immunised with different mixtures of mHABPs.A. Reactivity with CSP-derived 25608, 32958, and TRAP 24246 mHABP mixtures 140 days after first immunisation (80 days after 3rd or III80) showing reactivity in 2/8 Aotus with CSP-rI. B. Reactivity with CSP-derived 25608, 32958, and TRAP 24254 and 24246 mHABP mixtures evidencing reactivity with CSP-rII and with TRAP rII in 5/6 Aotus monkeys C. Reactivity with CSP-derived rI 25608, rII 32958, TRAP rII 24254, MSP-2 24112, EBA-175 RI 13790 and rII 24292 and AMA-1 10022.

Mentions: All monkey sera were used at 1:25 dilution for WB analysis. Three out of the eight monkeys’ sera immunised with the 25608+32958+24246 mixture in monkey trial A-01/12 reacted very strongly with CSP1 rI but very weakly with CSP1 rII in one monkey, no reactivity being observed with the TRAP rI fragment (Fig 2A). The opposite occurred in trial B/12 involving the 25608 + 32958 + 24246 +24254 mixture when weak reactivity occurred in 1/6 monkeys with CSP1-rI and strong reactivity with CSP rII in 3/6 monkeys (Fig 2B). Such variation may have been due to AoDRβ1* allele diversity in the small groups of monkeys in each trial; it should be noted that these were outbred trapped Aotus monkeys from different parts of the Colombian Amazon basin simulating HLA-DRβ1* genetic frequency distribution in the human population and that each immunological test detected different immunological characteristics (IFA native proteins and WB denatured molecules).


IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development.

Patarroyo ME, Bermúdez A, Alba MP, Vanegas M, Moreno-Vranich A, Poloche LA, Patarroyo MA - PLoS ONE (2015)

WB analysis showing the reactivity of Aotus immunised with different mixtures of mHABPs.A. Reactivity with CSP-derived 25608, 32958, and TRAP 24246 mHABP mixtures 140 days after first immunisation (80 days after 3rd or III80) showing reactivity in 2/8 Aotus with CSP-rI. B. Reactivity with CSP-derived 25608, 32958, and TRAP 24254 and 24246 mHABP mixtures evidencing reactivity with CSP-rII and with TRAP rII in 5/6 Aotus monkeys C. Reactivity with CSP-derived rI 25608, rII 32958, TRAP rII 24254, MSP-2 24112, EBA-175 RI 13790 and rII 24292 and AMA-1 10022.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400017&req=5

pone.0123249.g002: WB analysis showing the reactivity of Aotus immunised with different mixtures of mHABPs.A. Reactivity with CSP-derived 25608, 32958, and TRAP 24246 mHABP mixtures 140 days after first immunisation (80 days after 3rd or III80) showing reactivity in 2/8 Aotus with CSP-rI. B. Reactivity with CSP-derived 25608, 32958, and TRAP 24254 and 24246 mHABP mixtures evidencing reactivity with CSP-rII and with TRAP rII in 5/6 Aotus monkeys C. Reactivity with CSP-derived rI 25608, rII 32958, TRAP rII 24254, MSP-2 24112, EBA-175 RI 13790 and rII 24292 and AMA-1 10022.
Mentions: All monkey sera were used at 1:25 dilution for WB analysis. Three out of the eight monkeys’ sera immunised with the 25608+32958+24246 mixture in monkey trial A-01/12 reacted very strongly with CSP1 rI but very weakly with CSP1 rII in one monkey, no reactivity being observed with the TRAP rI fragment (Fig 2A). The opposite occurred in trial B/12 involving the 25608 + 32958 + 24246 +24254 mixture when weak reactivity occurred in 1/6 monkeys with CSP1-rI and strong reactivity with CSP rII in 3/6 monkeys (Fig 2B). Such variation may have been due to AoDRβ1* allele diversity in the small groups of monkeys in each trial; it should be noted that these were outbred trapped Aotus monkeys from different parts of the Colombian Amazon basin simulating HLA-DRβ1* genetic frequency distribution in the human population and that each immunological test detected different immunological characteristics (IFA native proteins and WB denatured molecules).

Bottom Line: Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures.They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR).Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response.

View Article: PubMed Central - PubMed

Affiliation: Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Universidad Nacional de Colombia, Bogotá, Colombia.

ABSTRACT
Determining immune protection-inducing protein structures (IMPIPS) involves defining the stereo-electron and topochemical characteristics which are essential in MHC-p-TCR complex formation. Modified high activity binding peptides (mHABP) were thus synthesised to produce a large panel of IMPIPS measuring 26.5 ±3.5Å between the farthest atoms fitting into Pockets 1 to 9 of HLA-DRβ1* structures. They displayed a polyproline II-like (PPIIL) structure with their backbone O and N atoms orientated to establish H-bonds with specific residues from HLA-DRβ1*-peptide binding regions (PBR). Residues having specific charge and gauche+ orientation regarding p3χ1, p5χ2, and p7χ1 angles determined appropriate rotamer orientation for perfectly fitting into the TCR to induce an appropriate immune response. Immunological assays in Aotus monkeys involving IMPIPS mixtures led to promising results; taken together with the aforementioned physicochemical principles, non-interfering, long-lasting, protection-inducing, multi-epitope, multistage, minimal subunit-based chemically-synthesised peptides can be designed against diseases scourging humankind.

Show MeSH
Related in: MedlinePlus