Invasion-inhibitory peptides chosen by natural selection analysis as an antimalarial strategy.

Plasmodium vivax's biological complexity has restricted in vitro culture development for characterising antigens involved in erythrocyte invasion and their immunological relevance. The murine model is proposed as a suitable alternative in the search for therapeutic candidates since Plasmodium yoelii uses homologous proteins for its invasion. The AMA-1 protein is essential for parasite invasion of erythrocytes as it is considered an important target for infection control. This study has focused on functional PyAMA-1 peptides involved in host-pathogen interaction; the protein is located in regions under negative selection as determined by bioinformatics analysis. It was found that pyama1 has two highly conserved regions amongst species (>70%) under negative selection. Fourteen synthetic peptides spanning both conserved regions were evaluated; 5 PyAMA-1 peptides having high specific binding (HABP) to murine erythrocytes were identified. The parasite's invasion inhibition capability was analysed through in vitro assays, suggesting that peptides 42681 (43-ENTERSIKLINPWDKYMEKY-62), 42903 (206-RYSSNDANNENQPFSFTPEK-225) and 42904 (221-FTPEKIENYKDLSYLTKNLR-240) had greater than 50% inhibition profile and restricted P. yoelii intra-erythrocyte development. This work proposes that the screening of conserved HABPs under negative selective pressure might be good candidates for developing a synthetic anti-malarial vaccine since they share functionally-relevant characteristics, such as interspecies conservation, specific RBC binding profile, invasion and parasite development inhibition capability, and the predicted B-epitopes within were recognised by sera obtained from experimentally-infected mice.

Molecular characterisation of parvorder Platyrrhini IgG sub-classes.

Non-human primates (NHP) are essential in modern biomedical research; New World monkeys (NWM) are mainly used as an experimental model regarding human malaria as they provide useful information about the parasite's biology and an induced immune response. It is known that a vaccine candidate's efficacy is mediated by a protection-inducing antibody response (IgG). Not enough information is available concerning IgG subclasses' molecular characteristics regarding NHP from parvorder Platyrrhini. Understanding the nature of the humoral immune response and characterising the IgG subclasses' profile will provide valuable information about the immunomodulator mechanisms of vaccines evaluated using an NHP animal model. This article has characterised IgG subclasses in NWM (i.e. genera Aotus, Cebus, Ateles and Alouatta) based on the amplification, cloning and sequencing of the immunoglobulin heavy constant gamma (IGHG) gene's CH1 to CH3 regions. The resulting sequences enabled elucidating IGHG gene organisation; two IgG variants were found in the Aotus and Ateles monkey group and three IgG variants in the Cebus and Alouatta group. The sequences were highly conserved in Platyrrhini and had a similar structure to that reported for monkeys from parvorder Catarrhini. Such information will help in developing tools for a detailed characterisation of the humoral immune response in an NWM experimental animal model.

A comparative analysis of SLA-DRB1 genetic diversity in Colombian (creoles and commercial line) and worldwide swine populations.

Analysing pig class II mayor histocompatibility complex (MHC) molecules is mainly related to antigen presentation. Identifying frequently-occurring alleles in pig populations is an important aspect to be considered when developing peptide-based vaccines. Colombian creole pig populations have had to adapt to local conditions since entering Colombia; a recent census has shown low amounts of pigs which is why they are considered protected by the Colombian government. Commercial hybrids are more attractive regarding production. This research has been aimed at describing the allele distribution of Colombian pigs from diverse genetic backgrounds and comparing Colombian SLA-DRB1 locus diversity to that of internationally reported populations. Twenty SLA-DRB1 alleles were identified in the six populations analysed here using sequence-based typing. The amount of alleles ranged from six (Manta and Casco Mula) to nine (San Pedreño). Only one allele (01:02) having > 5% frequency was shared by all three commercial line populations. Allele 02:01:01 was shared by five populations (around > 5% frequency). Global FST indicated that pig populations were clearly structured, as 20.6% of total allele frequency variation was explained by differences between populations (FST = 0.206). This study's results confirmed that the greatest diversity occurred in wild boars, thereby contrasting with low diversity in domestic pig populations.