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.
Highlights
Chemical and physical knowledge accumulated over the last five decades at subatomic level regarding the microbe’s most relevant molecules involved in invasion and infection and the human host’s immune system molecules’ biological and structural information has provided a solid background for promoting chemically-synthesised vaccines
VHLLAI Modified high activity binding peptides (mHABP) in complete antimalarial vaccine mixture development
Since complete protective immunity is a very complex mechanism involving many mHABPs derived from numerous proteins involved in host invasion during several development stages, we started the search for appropriate mHABP mixtures, trying to include most HLA-DRβ1Ã allele-specific ones
Summary
Chemical and physical knowledge accumulated over the last five decades at subatomic level regarding the microbe’s most relevant molecules involved in invasion and infection and the human host’s immune system molecules’ biological and structural information has provided a solid background for promoting chemically-synthesised vaccines.
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