Detection of antibodies against flavivirus over time in wild non-human primates from the lowlands of Costa Rica.

Two-hundred-nine free ranging non-human primates from 31 locations throughout Costa Rica were captured and released between 1993 and 2012, and blood samples, sera or plasma were collected, to detect antigens and antibodies, and so assess the distribution of active and passive flavivirus infections over time. A competitive enzyme-linked immunoassay for the detection of antibodies was used to determine the distribution of past flavivirus infections over time, while Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was used to detect active West Nile Virus (WNV) and Dengue virus (DENV) infections. The first serological evidence of flavivirus in these animals was determined in 1993, at the same time when DENV re-emerged in humans from Costa Rica. An increase in the number of seropositive wild monkeys to flavivirus was determined over time in the country (11.3% seropositivity in 1993-1996, 20.7% in 2001-2008, and finally 52.9% in 2010-2012). Furthermore, the presence of DENV2 was detected in samples from four howler monkeys collected in 2001-2002, whereas DENV2, DENV3, and DENV4 were found in samples from four white-faced monkeys, and WNV in three howler monkeys living in the Pacific coast of Costa Rica during 2010-2012. The habitat where the positive PCR individuals lived were characterized as fragmented forests, having temperatures ranging from 26°C to 28°C, altitudes below 250 meters above sea level, high precipitation during 7 to 9 months (1500-4000 mm), and a marked dry season of 3 to 5 months. All these animals were living near mangroves; however, they did not show clinical signs of illness at the time of sampling. Results obtained show that the number of seropositive wild non-human primates to flavivirus were increasing during time in the country, longitudinal studies are needed to investigate their role as sentinels of these viruses and to determine if flavivirus infections can affect these species.

Characterization and antigenicity of the promising vaccine candidate Plasmodium vivax 34kDa rhoptry antigen (Pv34).

This study describes the identification of the Plasmodium vivax rhoptry antigen Pv34 whose sequence was obtained based on homology comparison with the Plasmodium falciparum Pf34. The pv34 gene product was characterized by molecular biology and immunological techniques. Additionally, association of Pv34 to detergent-resistant microdomains (DRMs), expression in late blood-stage parasites and recognition of recombinant Pv34 (rPv34) by sera from P. vivax-infected Aotus monkeys and patients was assessed. Lymphoproliferation and cytokine secretion was also evaluated in individuals living in malaria endemic areas. Altogether, the data support carrying out further studies to assess the immunogenicity and protection-inducing ability of rPv34 as component of a multi-antigenic, multi-stage vaccine against vivax malaria.

Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

Aotus is one of the WHO-recommended primate models for studies in malaria, and several species can be infected with Plasmodium falciparum or P. vivax. Here we describe the successful infection of the species A. infulatus from eastern Amazon with blood stages of P. falciparum. Both intact and splenectomized animals were susceptible to infection; the intact ones were able to keep parasitemias at lower levels for several days, but developed complications such as severe anemia; splenectomized monkeys developed higher parasitemias but no major complications. We conclude that A. infulatus is susceptible to P. falciparum infection and may represent an alternative model for studies in malaria.

Pulmonary biology of anti-interleukin 5 antibodies

Interleukin 5 (IL-5) is a critical cytokine for the maturation of eosinophil precursors to eosinophils in the bone marrow and those eosinophils then accumulate in the lungs during asthma. We have studied anti-bodies on allergic responses in mice, guinea pigs anf monkeys and are extending this experiment into humans with a humanized antibody. In a monkey model of pulmonary inflammation and airway hyperreactivity, we found that the TRFK-5 antibody blocked both responses for three months following a single dose of 0.3 mg/kg i.v. This antibody also blocked lung eosinophilia in mice by inhibiting release from the bone marrow. To facilitate multiple dosing and to reduce immunogenicity in humans, we prepared Sch 55700, humanized antibody against IL-5. Sch 55700 was also active against lung eosinophilia in allergic monkeys and mice and against pulmonary eosinophilia and airway hyperresponsiveness in guinea pigs. Furthermore, as opposed to steroids, Sch 55700 dis not cause immunosuppression in guinea pigs. Studies with antibody in humans will be critical to establishing the therapeutic potential of IL-5 inhibition.

Comparative mitogen responses of lymphocytes from Colombian Panamanian, and Peruvian owl monkeys.

A comparative study of lymphocyte responses to various mitogens, an index of cell-mediated immune competency, was made under various culture conditions using peripheral blood lymphocytes from Colombian, Panamanian, and Peruvian Aotus monkeys. Dose response curves were determined for each primate group to phytohemagglutinin, concanavalin A, and pokeweed mitogen stimulation. Considerable variation in mitogen response was observed. The influence of culture media supplemented with fetal calf serum or autologous plasma, the number of cells per culture, and the duration of incubation on mitogen responsiveness was also evaluated. Optimal lymphocyte culture conditions also differed among the three groups. Owl monkeys from the same location in South and Central America showed similar responses to physical condition and free of detectable disease, these differences probably reflect fundamental inherent biological differences between subpopulations of owl monkeys.