RESUMO
A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRß* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRß* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component. Their identification (through 1H-NMR and Aotus monkey immunization) and proper modification contributes to a logical and rational methodology for long-lasting and protective immunological memory.
Assuntos
Cadeias HLA-DRB1/química , Cadeias HLA-DRB1/imunologia , Vacinas Antimaláricas/química , Vacinas Antimaláricas/imunologia , Peptídeos/química , Peptídeos/imunologia , Animais , Aotidae , Sítios de Ligação , Peptídeos/síntese químicaRESUMO
A totally effective, antimalarial vaccine must involve sporozoite and merozoite proteins (or their fragments) to ensure complete parasite blocking during critical invasion stages. This Special Report examines proteins involved in critical biological functions for parasite survival and highlights the conserved amino acid sequences of the most important proteins involved in sporozoite invasion of hepatocytes and merozoite invasion of red blood cells. Conserved high activity binding peptides are located in such proteins' functionally strategic sites, whose functions are related to receptor binding, nutrient and protein transport, enzyme activity and molecule-molecule interactions. They are thus excellent targets for vaccine development as they block proteins binding function involved in invasion and also their biological function.
Assuntos
Antígenos de Protozoários/metabolismo , Eritrócitos/parasitologia , Hepatócitos/parasitologia , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Animais , Cristalografia por Raios X , Desenho de Fármacos , Eritrócitos/imunologia , Hepatócitos/imunologia , Interações Hospedeiro-Patógeno , Humanos , Espectroscopia de Ressonância MagnéticaRESUMO
Malaria parasites have their Achilles' heel; they are vulnerable in small parts of their relevant molecules where they can be wounded and killed. These are sporozoite and merozoite protein conserved high activity binding peptides (cHABPs), playing a critical role in binding to and invasion of host cells (hepatocytes and erythrocytes, respectively). cHABPs can be modified by specific amino acid replacement, according to previously published physicochemical rules, to produce analogues (mHABPs) having left-handed polyproline II (PPIIL)-like structures which can modulate an immune response due to fitting perfectly into the HLA-DRß1* peptide binding region (PBR) and having an appropriate presentation to the T-cell receptor (TCR).