Aotus Nancymaae Research Articles

Pre-clinical Assessment of C134, a Chimeric Oncolytic Herpes Simplex Virus, in Mice and Non-human Primates

Oncolytic herpes simplex virus (oHSV) type I constructs are investigational anti-neoplastic agents for a variety of malignancies, including malignant glioma. Clinical trials to date have supported the safety of these agents even when directly administered in the CNS. Traditional pre-clinical US Food and Drug Administration (FDA) toxicity studies for these agents have included the use of two species, generally including murine and primate studies. Recently, the FDA has decreased its requirement of non-human primates as an animal model for ethical reasons, especially for established viral systems where there are good alternative model systems. Here we present data demonstrating the safety of C134, a chimeric oHSV construct, in CBA mice as well as in a limited number of the HSV-sensitive non-human primate Aotus nancymaae as a proposed agent for clinical trials. These data, along with the previously conducted clinical trials of oHSV constructs, support the use of the CBA mouse model as sufficient for the pre-clinical toxicity studies of this agent. We summarize our experience with different HSV recombinants and differences between them using multiple assays to assess neurovirulence, as well as our experience with C134 in a limited number of A. nancymaae.

Disappearing in the Night: An Overview on Trade and Legislation of Night Monkeys in South and Central America

The international trade in night monkeys (Aotus spp.), found throughout Central and South America, has been regulated by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) since 1975. We present a quantitative analysis of this trade from all 9 range countries, over 4 decades, and compare domestic legislation to CITES regulations. Night monkeys were exported from 8 of the 9 habitat countries, totalling 5,968 live individuals and 7,098 specimens, with trade of live individuals declining over time. In terms of species, the most commonly traded was Aotus nancymaae (present in Brazil, Colombia, Peru) followed by A. vociferans (Brazil, Colombia, Ecuador, Peru) and A. zonalis (Colombia, Panama). There was no significant correlation between levels of trade and species' geographic range size or the number of countries in which a species occurs. Five countries have legislation that meets CITES requirements for implementation, whereas the other 4 countries' legislation showed deficiencies. Research conducted in Colombia, Peru, and Brazil suggests significant cross-border trade not captured in official international trade registers. Although international trade has diminished, current trends suggest that populations of rarer species may be under unsustainable pressure. Further research is needed to quantify real trade numbers occurring between habitat countries.

The Aotus nancymaae erythrocyte proteome and its importance for biomedical research

The Aotus nancymaae species has been of great importance in researching the biology and pathogenesis of malaria, particularly for studying Plasmodium molecules for including them in effective vaccines against such microorganism. In spite of the forgoing, there has been no report to date describing the biology of parasite target cells in primates or their biomedical importance. This study was thus designed to analyse A. nancymaae erythrocyte protein composition using MS data collected during a previous study aimed at characterising the Plasmodium vivax proteome and published in the pertinent literature. Most peptides identified were similar to those belonging to 1189 Homo sapiens molecules; >95% of them had orthologues in New World primates. GO terms revealed a correlation between categories having the greatest amount of proteins and vital cell function. Integral membrane molecules were also identified which could be possible receptors facilitating interaction with Plasmodium species. The A. nancymaae erythrocyte proteome is described here for the first time, as a starting point for more in-depth/extensive studies. The data reported represents a source of invaluable information for laboratories interested in carrying out basic and applied biomedical investigation studies which involve using this primate. SignificanceAn understanding of the proteomics characteristics of A. nancymaae erythrocytes represents a fascinating area for research regarding the study of the pathogenesis of malaria since these are the main target for Plasmodium invasion. However, and even though Aotus is one of the non-human primate models considered most appropriate for biomedical research, knowledge of its proteome, particularly its erythrocytes, remains unknown. According to the above and bearing in mind the lack of information about the A. nancymaae species genome and transcriptome, this study involved a search for primate proteins for comparing their MS/MS spectra with the available information for Homo sapiens. The great similarity found between the primate's molecules and those for humans supported the use of the monkeys or their cells for continuing assays involved in studying malaria. Integral membrane receptors used by Plasmodium for invading cells were also found; this required timely characterisation for evaluating their therapeutic role. The list of erythrocyte protein composition reported here represents a useful source of basic knowledge for advancing biomedical investigation in this field.

Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys

Malaria is a disease caused by a protozoan of the Plasmodium genus and results in 0.5–0.7million deaths per year. Increasing drug resistance of the parasite and insecticide resistance of mosquitoes necessitate alternative control measures. Numerous vaccine candidates have been identified but none have been able to induce robust, long-lived protection when evaluated in malaria endemic regions. Rodent studies have demonstrated that chemically attenuated blood stage parasites can persist at sub-patent levels and induce homologous and heterologous protection against malaria. Parasite-specific cellular responses were detected, with protection dependent on CD4+ T cells. To investigate this vaccine approach for Plasmodium falciparum, we characterised the persistence and immunogenicity of chemically attenuated P. falciparum FVO strain parasites (CAPs) in non-splenectomised Aotus nancymaae monkeys following administration of a single dose. Control monkeys received either normal red blood cells or wild-type parasites followed by drug treatment. Chemical attenuation was performed using tafuramycin A, which irreversibly binds to DNA. CAPs were detected in the peripheral blood for up to 2days following inoculation as determined by thick blood smears, and for up to 8days as determined by quantitative PCR. Parasite-specific IgG was not detected in monkeys that received CAPs; however, in vitro parasite-specific T cell proliferation was observed. Following challenge, the CAP monkeys developed an infection; however, one CAP monkey and the infection and drug-cure monkeys showed partial or complete resistance. These experiments lay the groundwork for further assessment of CAPs as a potential vaccine against malaria.

Socialization of adult owl monkeys (Aotus sp.) in Captivity.

Social housing has often been recommended as one-way to address the psychological well-being of captive non-human primates. Published reports have examined methods to socialize compatible animals by forming pairs or groups. Successful socialization rates vary depending on the species, gender, and environment. This study presents a retrospective look at pairing attempts in two species of owl monkeys, Aotus nancymaae and A. azarae, which live in monogamous pairs in the wild. The results of 477 pairing attempt conducted with captive, laboratory housed owl monkeys and 61 hr of behavioral observations are reported here. The greatest success pairing these owl monkeys occurred with opposite sex pairs, with an 82% success rate. Opposite sex pairs were more successful when females were older than males. Female-female pairs were more successful than male-male (MM) pairs (62% vs 40%). Successful pairs stayed together between 3 and 7 years before the animals were separated due to social incompatibility. Vigilance, eating, and sleeping during introductions significantly predicted success, as did the performance of the same behavior in both animals. The results of this analysis show that it is possible to give captive owl monkeys a social alternative even if species appropriate social partners (i.e., opposite sex partners) are not available. The focus of this report is a description of one potential way to enhance the welfare of a specific new world primate, the owl monkey, under laboratory conditions. More important is how the species typical social structure of owl monkeys in nature affects the captive management of this genus. Am. J. Primatol. 79:e22521, 2017. © 2015 Wiley Periodicals, Inc.

Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates

Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach.

Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates.

Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals from captive owl monkey populations harbor CD4 alleles that are compatible with a broad collection of HIV-1 isolates, including those isolated from early in infection in highly affected populations and representing diverse subtypes.

Cortical inputs to the middle temporal visual area in New World owl monkeys.

We made eight retrograde tracer injections into the middle temporal visual area (MT) of three New World owl monkeys (Aotus nancymaae). These injections were placed across the representation of the retina in MT to allow us to compare the locations of labeled cells in other areas in order to provide evidence for any retinotopic organization in those areas. Four regions projected to MT: 1) early visual areas, including V1, V2, V3, the dorsolateral visual area, and the dorsomedial visual area, provided topographically organized inputs to MT; 2) all areas in the MT complex (the middle temporal crescent, the middle superior temporal area, and the fundal areas of the superior temporal sulcus) projected to MT. Somewhat variably across injections, neurons were labeled in other parts of the temporal lobe; 3) regions in the location of the medial visual area, the posterior parietal cortex, and the lateral sulcus provided other inputs to MT; 4) finally, projections from the frontal eye field, frontal visual field, and prefrontal cortex were also labeled by our injections. These results further establish the sources of input to MT, and provide direct evidence within and across cases for retinotopic patterns of projections from early visual areas to MT.

Protective Efficacy of a Plasmodium vivax Circumsporozoite Protein-Based Vaccine in Aotus nancymaae Is Associated with Antibodies to the Repeat Region

We have previously reported that Vivax Malaria Protein 001 (VMP001), a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax, is immunogenic in mice and rhesus monkeys in the presence of various adjuvants. In the present study, we evaluated the immunogenicity and efficacy of VMP001 formulated with a TLR9 agonist in a water-in-oil emulsion. Following immunization, the vaccine efficacy was assessed by challenging Aotus nancymaae monkeys with P. vivax sporozoites. Monkeys from both the low- and high-dose vaccine groups generated strong humoral immune responses to the vaccine (peak median titers of 291,622), and its subunits (peak median titers to the N-term, central repeat and C-term regions of 22,188; 66,120 and 179,947, respectively). 66.7% of vaccinated monkeys demonstrated sterile protection following challenge. Protection was associated with antibodies directed against the central repeat region. The protected monkeys had a median anti-repeat titer of 97,841 compared to 14,822 in the non-protected monkeys. This is the first report demonstrating P. vivax CSP vaccine-induced protection of Aotus monkeys challenged with P. vivax sporozoites.

Development of an Aotus nancymaae model for Shigella Vaccine immunogenicity and efficacy studies.

Several animal models exist to evaluate the immunogenicity and protective efficacy of candidate Shigella vaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenic Escherichia coli (ETEC) and Campylobacter spp. have been successfully developed with Aotus nancymaae, and the addition of a Shigella-Aotus challenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose of Shigella flexneri 2a strain 2457T that induces an attack rate of 75% in the Aotus monkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 10(11) CFU. Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologous Shigella serotype. A successive study in A. nancymaae evaluated the ability of multiple oral immunizations with live-attenuated Shigella vaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged with S. flexneri 2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%; P = 0.05). The overall study results indicate that the Shigella-Aotus nancymaae challenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection.

Research and in situ conservation of owl monkeys enhances environmental law enforcement at the Colombian‐Peruvian border

This study reports on impacts of illegal trade in owl monkeys (Aotus nancymaae, A. vociferans) for the biomedical research market in the Colombian-Peruvian Amazonian border. Through freedom of information requests and interviews with hunters we found that 912 owl monkeys, including A. nancymaae captured in Peru, were trapped over a 3-month period in 2012 to supply a malaria research facility based in Leticia, Colombia, which had trapping permits for the use of only 800 A. vociferans annually yet experimentation took place using A. nancymaae. High levels of extraction in Peru have had population-level impacts with significantly lower densities of Aotus spp. (3-24 individuals/km(2)) compared to Colombian sites with low hunting pressure (26-44 individuals/km(2)). Post-experimental release of this species in Colombian territory has created a new distribution whose status and impacts on resident populations of A. vociferans remain unknown. The trapping method has also had environmental impact, with loss of over 65,000 trees (including sleeping sites), annually. As Aotus species are registered under the Convention of International Trade in Endangered Species of Wild Fauna and Flora (CITES) Appendix II, international trade requires official permission and evidence that extraction does not impact wild populations. However, no official records exist and CITES legislation has failed, due principally to a lack of appropriate monitoring by national authorities responsible for compliance. Of further concern is that we had previously documented and reported the illegal trade to the appropriate governmental authorities yet still no action was taken-as demonstrated by the continuing trade in 2013. Enforcement eventually occurred when a non-governmental organization initiated legal action against organizations responsible. A successful second instance ruling by the Colombian State's Council in 2013 revoked trapping permits. Using the trade in owl monkeys as a case study we consider implementation, compliance, and enforcement of CITES in the border area to identify mechanisms to improve enforcement of environmental legislation.

PfRH5 vaccine efficacy against heterologous strain blood-stage Plasmodium falciparum

BackgroundThere is a need for a more effective vaccine against Plasmodium falciparum than the current leading candidate, RTS,S. Vaccines against the parasite's asexual blood-stage might reduce mortality, morbidity, and transmission of malaria, but face problems of antigenic polymorphism and the apparent requirement for exceptionally high antibody concentrations to achieve protection. We recently reported that vaccines based on the blood-stage merozoite antigen PfRH5 induce antibodies capable of strain-transcending in-vitro growth inhibition activity (GIA). Here, we report the results of a study of vaccination of non-human primates followed by challenge with P falciparum. MethodsNon-human primates (Aotus nancymaae) were vaccinated with PfRH5 vaccine formulations (including PfRH5 protein in Freund's adjuvant and an adenovirus/poxvirus viral vector regimen) based on the 3D7 strain of P falciparum, and challenged with the heterologous P falciparum FVO strain. Control animals were given vaccines that did not contain a malaria antigen. The primary vaccine efficacy endpoints were the need for antimalarial treatment compared with historical controls in the PfRH5-Freund's group; and in the viral vector group, cumulative parasitaemia to day 10 of the study was compared with control animals challenged after receiving vaccines lacking a malaria antigen. As well as vaccine-induced protection against the challenge, antigen-specific antibody concentration, parasite-neutralising antibody (GIA), and cellular immune responses were assessed. FindingsSix of six animals vaccinated with PfRH5 in Freund's adjuvant and four of six animals vaccinated with human-compatible PfRH5 viral vector vaccines survived the challenge without reaching an endpoint requiring treatment, and without clinically evident symptoms of malaria, compared with none of six control animals (p<0·001 for vaccine efficacy in both groups vs controls, Mann-Whitney U test). There was a strong correlation between cumulative parasitaemia to day 10 and both antigen-specific antibody concentration and parasite-neutralising antibody activity (Spearman rank correlation coefficient r=−0·82 and −0·92, respectively; p<0·0001 for both). InterpretationThese results are the first, to our knowledge, to show protection against blood-stage malaria by a human-compatible vaccine and the first to show strain-transcending protection in this highly stringent challenge model; furthermore, they show that an antigen selected on the basis of in-vitro neutralisation assays can induce in-vivo protection. PfRH5-based vaccines are now entering clinical development. There is a need to assess the efficacy of these vaccines in man, to assess the longevity of vaccine-induced protection, and to formally assess protection by passively transferred parasite-neutralising antibody. FundingWellcome Trust, UK Medical Research Council, Isis Innovations.

Various PfRH5 polymorphisms can support Plasmodium falciparum invasion into the erythrocytes of owl monkeys and rats

Aotus nancymaae, the owl monkey, provides a useful laboratory model for research to develop drugs and vaccines against human falciparum malaria; however, many Plasmodium falciparum parasites are unable to invade A. nancymaae erythrocytes, rendering the parasites noninfective to the monkeys. In previous work, we identified a key polymorphism that determined the inheritance of erythrocyte invasion in a genetic cross of two P. falciparum clones that were virulent (GB4) or noninfective (7G8) to A. nancymaae. This polymorphism, an isoleucine-to-lysine polymorphism at position 204 (I204K) of the GB4 erythrocyte binding protein PfRH5, was nevertheless not found in several other P. falciparum lines that could also invade A. nancymaae erythrocytes. Alternative PfRH5 polymorphisms occur at different positions in these virulent parasites, and additional polymorphisms are found in P. falciparum parasites that cannot infect A. nancymaae. By allelic replacement methods, we have introduced the polymorphisms of these A. nancymaae-virulent or noninfective parasites at codons 204, 347, 358, 362, 410, and 429 of the endogenous PfRH5 gene in the noninfective 7G8 line. 7G8 transformants expressing the polymorphisms of the A. nancymaae-virulent parasites show neuraminidase-sensitive (sialic acid-dependent) invasion into the monkey erythrocytes, whereas 7G8 transformants expressing the PfRH5 alleles of noninfective parasites show little or no invasion of these erythrocytes. Parasites harboring PfRH5 polymorphisms 204K or 204R are also able to invade rat erythrocytes and are differentially sensitive to the removal of surface sialic acids by neuraminidase. These studies offer insights into the PfRH5 receptor-binding domain and interactions that support the invasion of various primate and rodent erythrocytes by P. falciparum.

Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum

Event Abstract Back to Event Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum Alexander D. Douglas1*, Andrew R. Williams1, Joseph J. Illingworth1, Kathryn A. Hjerrild1 and Simon J. Draper1 1 University of Oxford, Jenner Institute, Nuffield Department of Medicine, United Kingdom There is a need for a more effective vaccine against P. falciparum than the current leading candidate, RTS,S. Vaccines against the parasite’s asexual blood-stage may reduce mortality, morbidity and transmission of malaria, but face problems of antigenic polymorphism and the apparent requirement for exceptionally high antibody levels to achieve protection. We recently reported that vaccines based upon the blood-stage merozoite antigen PfRH5 induce antibodies capable of strain-transcending in vitro growth inhibition activity (GIA). Here we will now describe cross-strain protection achieved by these vaccines in the stringent Aotus nancymaae non-human primate – P. falciparum challenge model, which correlates strongly with vaccine-induced pre-challenge GIA and total IgG anti-PfRH5 ELISA titres. This is the first example of clinically meaningful cross-strain protection of Aotus by a human-compatible blood-stage vaccine regime, and supports the strategy of vaccine selection using in vitro GIA. We will also describe work to characterise the mechanism of parasite neutralisation by anti-PfRH5 antibodies. This includes generation of novel monoclonal antibodies with neutralisation potency among the highest described for any anti-merozoite antibody, and mapping of minimal linear epitopes for two of these. We will present data which suggest that fine epitope specificity and interaction kinetics are more important determinants of neutralisation potency than ability to block the interaction between PfRH5 and its receptor, basigin. These data shed important insight on the mechanism of blood-stage malaria parasite neutralisation, and support the continued clinical development of PfRH5-based vaccines. Phase Ia clinical trials of PfRH5 vaccine candidates are due to commence in Oxford in 2014. Keywords: Malaria, Falciparum, Malaria Vaccines, PfRh5, Antibodies, viral vector vaccines Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Douglas AD, Williams AR, Illingworth JJ, Hjerrild KA and Draper SJ (2013). Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00574 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Alexander D Douglas, University of Oxford, Jenner Institute, Nuffield Department of Medicine, Oxford, OX3 7DQ, United Kingdom, sandy.douglas@ndm.ox.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Google Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Google Scholar Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper PubMed Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae.

BackgroundRabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP). To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus.MethodsEight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R) and observed for >130 days. Oral and blood samples were collected and analyzed.ResultsTwo monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D.) was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429). No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody.DiscussionThis study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically apparent disease and prolonged in cases infected at sites further from the brain.ConclusionsOur findings support the hypothesis that a viremic state for rabies does not exist in the New World Monkey, Aotus nancymaae, and it appears that this species may be refractory to infection. The species does provide a suitable model to assess post infection immune responses. Additional studies that address the limitations of sample size, length of observation, and lack of measurable infection should be conducted.

Mammalian Diversity and Matses Ethnomammalogy in Amazonian Peru Part 1: Primates

This report is the first installment of a monographic study of mammalian diversity and ethnomammalogy in a sparsely inhabited rainforest region between the Yavarí and Ucayali rivers in northeastern Peru. Our study is based on several large collections of mammals (totaling about 3500 specimens) made at various localities in this region between 1926 and 2003, and on our long-term ethnobiological and linguistic fieldwork with the Matses, a Panoan-speaking group of indigenous Amazonians who still obtain most of their dietary protein by hunting mammals. Our primary objectives are to document the species richness of the regional fauna through taxonomic analysis of collected specimens, and to assess the detail and accuracy of Matses knowledge of mammalian natural history by linguistic analysis of recorded interviews.The regional primate fauna is definitely known to consist of at least 14 species documented by collected specimens and/or repeated sightings of taxa with visually conspicuous diagnostic traits. This fauna includes three atelids (Alouatta seniculus, Ateles belzebuth, Lagothrix lagothricha), eight cebids (Aotus nancymaae, Callimico goeldii, Callithrix pygmaea, Cebus albifrons, Cebus apella, Saguinus fuscicollis, Saguinus mystax, Saimiri sciureus), and three pitheciids (Cacajao calvus, Callicebus cupreus, Pithecia monachus). All 14 species are known to occur sympatrically at one inventory site, but Goeldi's monkey (Callimico goeldii) is rare and uakaris (Cacajao calvus) seem to be patchily distributed, so some local faunas may have only 12 or even fewer species. This regional fauna is unique because neighboring interfluvial regions lack some species that are present in the Yavarí-Ucayali interfluve, and because some species that are present in neighboring interfluvial regions are not known to occur between the Yavarí and the Ucayali.Matses knowledge about primate natural history is clearly correlated with size and cultural importance. For example, information obtained from standardized interviews about spider monkeys (Ateles belzebuth, a large game species) can be parsed into 86 observations about its ecology and/or behavior, whereas interviews about pygmy marmosets (Callithrix pygmaea, a small nongame species) contain only nine observations on these topics. Item-by-item comparisons of Matses observations about spider monkeys with the published results of scientific field research suggests that the Matses are generally accurate observers of primate natural history, a conclusion that is additionally supported by comparing community patterns of resource use compiled from our interview data with community-ecological studies of primate faunas in the scientific literature. Most exceptions (discrepancies between Matses observations and the scientific literature) can be explained by cultural inattention to small nongame species.Although these results suggest that archiving native Amazonian knowledge about mammalian natural history might be a cost-effective alternative to lengthy fieldwork for some research objectives, there are significant linguistic barriers than can inhibit effective cross-cultural communication. Among the Matses, these include a surprisingly large number of zoologically redundant names (synonyms and hyponyms). Relevant primate examples are discussed in substantive detail.

Immunogenicity and protective efficacy of a psoralen-inactivated dengue-1 virus vaccine candidate in Aotus nancymaae monkeys

Psoralens are photoreactive compounds that cross-link pyrimidines after exposure to UVA radiation. In this experiment, we tested the protective efficacy of a psoralen-inactivated dengue vaccine candidate in non-human primates. Two groups of 7 Aotus nancymaae monkeys received either 10 ng per dose of inactivated DENV1 plus alum adjuvant or alum alone (controls). Doses were injected intradermally on days 0, 14, and 28. Monkeys then received a challenge inoculation of 1.1 × 10 4 PFUs of WestPac 74 DENV-1 on day 132. At 62 days, only 1/7 vaccinated monkeys had detectable IgM, but IgG and neutralizing antibody remained detectable in 7/7. No IgM, IgG, or neutralizing antibody was detectable in control monkeys. DENV-1 viremia was detected after challenge in 3/7 vaccinated monkeys and 5/6 control monkeys (with one removed due to pregnancy) ( p = 0.27), but days of viremia were reduced from 3.67 days/animal among controls to 0.71 days/animal among vaccinated monkeys ( p = 0.051). Psoralen-inactivated DENV1 is immunogenic in Aotus nancymaae with a trend towards a reduction in days of viremia following experimental challenge.

Characterisation and comparative analysis of MHC-DPA1 exon 2 in the owl monkey ( Aotus nancymaae)

The Aotus nancymaae (owl monkey) is an important animal model in biomedical research, particularly for the preclinical evaluation of vaccine candidates against Plasmodium falciparum and Plasmodium vivax, which require a precisely typed major histocompatibility complex. The exon 2 from A. nancymaae MHC-DPA1 gene was characterised in order to infer its allelic diversity and evolutionary history. Aona-DPA1 shows no polymorphism and is related to other primate DPA alleles (including Catarrhini and Platyrrhini), constituting an ancient trans-specific and strongly supported lineage with different variability and selective patterns when compared to other primate–MHC-DPA1 lineages. A. nancymaae monkeys have thus a smaller MHC-DP polymorphism than MHC-DQ or MHC-DR.

Identification, classification and evolution of owl monkeys (Aotus, Illiger 1811).

BackgroundOwl monkeys, belonging to the genus Aotus, have been extensively used as animal models in biomedical research but few reports have focused on the taxonomy and phylogeography of this genus. Moreover, the morphological similarity of several Aotus species has led to frequent misidentifications, mainly at the boundaries of their distribution. In this study, sequence data from five mitochondrial regions and the nuclear, Y-linked, SRY gene were used for species identification and phylogenetic reconstructions using well characterized specimens of Aotus nancymaae, A. vociferans, A. lemurinus, A. griseimembra, A. trivirgatus, A. nigriceps, A. azarae boliviensis and A. infulatus.ResultsThe complete MT-CO1, MT-TS1, MT-TD, MT-CO2, MT-CYB regions were sequenced in 18 Aotus specimens. ML and Bayesian topologies of concatenated data and separate regions allowed for the proposition of a tentative Aotus phylogeny, indicating that Aotus diverged some 4.62 Million years before present (MYBP). Similar analyses with included GenBank specimens were useful for assessing species identification of deposited data.ConclusionsAlternative phylogenetic reconstructions, when compared with karyotypic and biogeographic data, led to the proposition of evolutionary scenarios questioning the conventional diversification of this genus in monophyletic groups with grey and red necks. Moreover, genetic distance estimates and haplotypic differences were useful for species validations.

Mated pairs of owl monkeys (Aotus nancymaae) exhibit sex differences in response to unfamiliar male and female conspecifics

In socially monogamous species, mate-guarding could be a reproductive strategy that benefits both males and females, especially when males contribute to parental care. By actively guarding mates, males may reduce their chances of being cuckolded, whereas females that mate-guard may reduce the likelihood that their mates will desert them or acquire additional mates, and hence limit or reduce paternal care of offspring. Owl monkeys (Aotus spp.) are socially monogamous with biparental care of young and, hence, potential beneficiaries of mate-guarding. We presented mated pairs of captive owl monkeys (A. nancymaae) with unfamiliar male and female conspecifics, to determine if either member of the pair exhibits intraspecific aggression toward an intruder or stays close to its mate, behaviors indicative of mate-guarding. Male mates were more responsible for the maintenance of close proximity between mates than females. Male mates also exhibited elevated levels of behavior that signify arousal when presented with a male conspecific. These responses by mated male owl monkeys are consistent with patterns that may help prevent cuckoldry.