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Raul Rodriguez

Publications and source records attributed to Raul Rodriguez.

6 recordsLinked to original sources
PubMed2004

Induction and displacement of an helix in the 6725 SERA peptide analogue confers protection against P. falciparum malaria.

The protein called serine repeat antigen (SERA) is a Plasmodium falciparum malaria antigen; high activity erythrocyte binding peptides have been identified in this protein. One of these, the 6725 peptide (non-immunogenic and non-protective), was analyzed for immunogenicity and protective activity in Aotus monkeys, together with several of its analogues. These peptides were studied by 1H NMR to try to correlate their structure with their biological function. These peptides showed helical regions having differences in their position, except for randomly structured 6725. It is shown that replacing some amino acids induced immunogenicity and protectivity against experimental malaria and changed their three-dimensional (3D) structure, suggesting that such modifications may allow a better fit with immune system molecules.

Amino Acid Sequence↗
PubMed2003

Splenectomised and spleen intact Aotus monkeys' immune response to Plasmodium vivax MSP-1 protein fragments and their high activity binding peptides.

Two E. coli expressed recombinant polypeptides (rPvMSP-1(14) and rPvMSP-1(20)) contained in the 33kDa fragment, located within Plasmodium vivax merozoite surface protein (PvMSP-1) 42kDa C-terminal region, and a cocktail of high reticulocyte binding synthetic peptides located within these fragments, were evaluated for immunogenicity and protective immune responses in splenectomised and spleen intact Aotus nancymaae monkeys. Thirty splenectomised monkeys who had been previously immunised with either rPvMSP-1(14), rPvMSP-1(20), or a mixture of both recombinant fragments were intravenously challenged with the heterologous P. vivax VCG-1 strain (as determined by DNA sequencing); full protection was observed in five monkeys and low parasitaemia levels were obtained in eight more monkeys. Splenectomised control monkey group rapidly developed high parasitaemia levels, while no significant parasitaemia was obtained in the non-splenectomised control group. Although PvMSP-1 42 and 33kDa fragments were recognised by Western Blot and whole parasites by IFAT when tested with immune monkey sera, no correlation between protection and antibody titres by IFAT and ELISA was observed, suggesting that protection is not being solely mediated by a humoral immune response. This data showed that partial protection against a heterologous strain challenge was best achieved when immunising with a rPvMSP-1(14)-rPvMSP-1(20) mixture (2 were fully protected and 4 with low parasitaemia out of 12) suggesting for the first time, that these fragments could be good candidates for inclusion in a P. vivax multi-stage, multi-antigen vaccine.

Amino Acid Sequence↗
PubMed2003

Distorting malaria peptide backbone structure to enable fitting into MHC class II molecules renders modified peptides immunogenic and protective.

The conserved, nonantigenic, nonimmunogenic malaria Merozoite Surface Protein-2 peptide 1, having high affinity for red blood cells, was rendered immunogenic and protective in Aotus monkeys by specifically changing some critical residues. The NMR structure revealed a switch from classical type III' into distorted III' and III beta turns in the protective peptides. These changes may lead to a better fit into the Aotus MHC class II human HLA-DRbeta1 12 molecule equivalent, thus activating the immune system.

Animals↗
PubMed2003

Modified merozoite surface protein-1 peptides with short alpha helical regions are associated with inducing protection against malaria.

The merozoite surface protein-1 represents a prime candidate for development of a malaria vaccine. Merozoite surface protein-1 has been shown to demonstrate high-activity peptide binding to human red blood cells. One of the high-activity binding peptides, named 5501, located in the N-terminus (amino acid sequence MLNISQHQCVKKQCPQNS) of the 19-kDa molecular mass fragment of merozoite surface protein-1, is conserved, nonimmunogenic and nonprotective. Its critical binding residues were identified and replaced with amino acids of similar mass but different charge, in order to modify their immunogenic and protective characteristics. Three analogues with positive or negative immunological results were studied by nuclear magnetic resonance to correlate their three-dimensional structure with their biological functions. The studied peptides presented alpha-helical fragments, but in different peptide regions and extensions, except for randomly structured 5501. We show that altering a few amino acids induced immunogenicity and protectivity against experimental malaria and changed the peptide three-dimensional structure, suggesting a better fit with immune-system molecules.

Amino Acid Sequence↗
PubMed2002

Sequence and expression of MHC-DPB1 molecules of the New World monkey Aotus nancymaae, a primate model for Plasmodium falciparum.

Aotus nancymaae represents an animal model for the pre-clinical evaluation of blood-stage vaccine candidates against Plasmodium falciparum and Plasmodium vivax. We present here the nucleotide sequences of exon 2 and 3 of MHC-DPB1 genes. In a group of seven unrelated animals captured in the wild, three alleles of MHC-DPB1 exon 2 could be identified. Phylogenetic analysis shows that in contrast to Aona- DRB and - DQB, the Aona-DPB1exon 2 amino acid sequences cluster in a species-specific manner. No evidence could be found for the conservation of allelic lineages pre-dating the divergence of Old and New World monkeys. Additionally, two nucleotide sequences of MHC-DPB1 exon 3 could be identified differing in one synonymous base exchange. Phylogenetic analysis of Aona-DPB1exon 3 amino acid sequence shows that it clusters together with human sequences separately from the New World monkey Saguinus oedipus. Aona-DP heterodimers are expressed on the surface of Aotus cells, as detected by staining with a cross-reactive monoclonal antibody, and can therefore present antigenic peptides to the cellular immune system.

Animals↗