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Rijswijk, Netherlands

Younga D.,Imperial College London | Verreck F.A.W.,Biomedical Primate Research Center
Tuberculosis | Year: 2012

The remarkable advances in TB vaccinology over the last decade have been driven by a pragmatic approach to moving candidates along the development pipeline to clinical trials, fuelled by encouraging data on protection in animal models. Efficacy data from Phase IIb trials of the first generation of new candidates are anticipated over the next 1-2 years. As outlined in the TB Vaccines Strategic Blueprint, to exploit this information and to inspire design of next generation candidates, it is important that this empirical approach is complemented by progress in understanding of fundamental immune mechanisms and improved translational modalities. Current trends towards improved experimental and computational approaches for studying biological complexity will be an important element in the developing science of TB vaccinology. © 2012 Elsevier Ltd. All rights reserved. Source


de Groot N.,Biomedical Primate Research Center
Immunogenetics | Year: 2014

A panel of 15 carefully selected microsatellites (short tandem repeats, STRs) has allowed us to study segregation and haplotype stability in various macaque species. The STRs span the major histocompatibility complex (MHC) region and map in more detail from the centromeric part of the Mhc-A to the DR region. Two large panels of Indian rhesus and Indonesian/Indochinese cynomolgus macaques have been subjected to pedigree analysis, allowing the definition of 161 and 36 different haplotypes and the physical mapping of 10 and 5 recombination sites, respectively. Although most recombination sites within the studied section of the Indian rhesus monkey MHC are situated between the Mhc-A and Mhc-B regions, the resulting recombination rate for this genomic segment is low and similar to that in humans. In contrast, in Indonesian/Indochinese macaques, two recombination sites, which appear to be absent in rhesus macaques, map between the class III and II regions. As a result, the mean recombination frequency of the core MHC, Mhc-A to class II, is higher in Indonesian/Indochinese cynomolgus than in Indian rhesus macaques, but as such is comparable to that in humans. The present communication demonstrates that the dynamics of recombination 'hot/cold spots' in the MHC, as well as their frequencies, may differ substantially between highly related macaque species. Source


Zeeman A.M.,Biomedical Primate Research Center
Methods in molecular biology (Clifton, N.J.) | Year: 2013

Long-term in vitro cultures of blood-stage parasites are so far feasible only for Plasmodium falciparum and P. knowlesi. In this chapter, we describe short-term ex vivo culturing of P. cynomolgi and P. vivax. We also describe long-term in vitro culturing of P. knowlesi as well as some techniques for synchronizing parasites. Cultured parasites can be used for a variety of purposes, e.g., for in vitro drug assays and antibody-mediated growth inhibition assays. Source


Persengiev S.,Biomedical Primate Research Center | Persengiev S.,University Utrecht | Kondova I.,Biomedical Primate Research Center | Otting N.,Biomedical Primate Research Center | And 2 more authors.
Neurobiology of Aging | Year: 2011

Neurodegenerative pathologies associated with aging exhibit clinical and morphological features that are relatively specific to humans. To gain insights into the evolution of the regulatory mechanisms of the aged brain, we compared age-related differences in microRNA (miRNA) expression levels in the cortex and cerebellum of humans, chimpanzees and rhesus macaques on a genome-wide scale. In contrast to global miRNA downregulation, a small subset of miRNAs was found to be selectively upregulated in the aging brain of all 3 species. Notably, miR-144 that is highly conserved appeared to be associated with the aging progression. Moreover, miR-144 plays a central role in regulating the expression of ataxin 1 (ATXN1), the disease-causing gene for the development spinocerebellar ataxia type 1 (SCA1). miRNA activity, including miR-144, -101 and -130 processing, was increased in the cerebellum and cortex of SCA1 and Alzheimer patients relative to healthy aged brains. Importantly, miR-144 and -101 inhibition increased ATXN1 levels in human cells. Thus, the activation of miRNA expression in the aging brain may serve to reduce the cytotoxic effect of polyglutamine expanded ATXN1 and the deregulation of miRNA expression may be a risk factor for disease development. © 2011 Elsevier Inc. Source


de Groot N.G.,Biomedical Primate Research Center | Bontrop R.E.,Biomedical Primate Research Center | Bontrop R.E.,University Utrecht
Retrovirology | Year: 2013

An HIV-1 infection progresses in most human individuals sooner or later into AIDS, a devastating disease that kills more than a million people worldwide on an annual basis. Nonetheless, certain HIV-1-infected persons appear to act as long-term non-progressors, and elite control is associated with the presence of particular MHC class I allotypes such as HLA-B*27 or -B*57. The HIV-1 pandemic in humans arose from the cross-species transmission of SIVcpz originating from chimpanzees. Chimpanzees, however, appear to be relatively resistant to developing AIDS after HIV-1/SIVcpz infection. Mounting evidence illustrates that, in the distant past, chimpanzees experienced a selective sweep resulting in a severe reduction of their MHC class I repertoire. This was most likely caused by an HIV-1/SIV-like retrovirus, suggesting that chimpanzees may have experienced long-lasting host-virus relationships with SIV-like viruses. Hence, if natural selection is allowed to follow its course, prospects for the human population may look grim, thus underscoring the desperate need for an effective vaccine. © 2013 de Groot and Bontrop; licensee BioMed Central Ltd. Source

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