Nonhuman primate (NHP) models will expedite therapeutics and vaccines for COVID-19 into clinical trials. We compared acute SARS-CoV-2 infection in young and old rhesus macaques and baboons and old marmosets. Macaques had clinical signs of viral infection, mild-to-moderate pneumonitis and extra-pulmonary pathologies; both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage (BAL) was increased in old versus young baboons. Using techniques like CT imaging, immunophenotyping, alveolar/peripheral cytokine responses and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent Type I-interferon response. Macaques developed T cell memory phenotype/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.
Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark for the use of DNA vaccine technology for the production of protective immune responses.
Despite the widespread use of bacillus Calmette-Gué rin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease very similar to humans, they have potential to provide important information in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we compared the efficacy of bacillus Calmette-Gué rin vaccination and the course of infection in both species. Unvaccinated rhesus and cynomolgus monkeys both developed progressive disease with high levels of C-reactive protein, M. tuberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette-Gué rin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a striking 2-log reduction in viable bacteria in the lungs compared with nonvaccinated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette-Gué rin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lungs. Comparative studies in these closely related species are likely to provide insight into mechanisms involved in protection against tuberculosis.T uberculosis (TB) is the leading global cause of death from a single infectious disease (1, 2), accelerated by the HIV epidemic and appearance of multidrug-resistant Mycobacterium tuberculosis (3). The efficiency of bacillus Calmette-Guérin, the only TB vaccine available for humans, ranges between 0 and 85% (4). Improved vaccines are needed urgently, and a large number of new TB vaccine candidates and delivery systems is being tested in small animal models (5-7). Human trials to evaluate new TB vaccines will be very complex, will often occur in bacillus Calmette-Guérin-immunized populations, will be of long duration, and require large cohorts (8). Effective screens to select only the most promising candidates, delivery systems, and formulations for clinical testing will be extremely valuable. Up to now, almost all efficacy testing of TB vaccine candidates has been in the mouse and͞or guinea pig (9). A more human-like response to TB has been described in the closely related rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques (reviewed in ref. 10). This similarity in response may be because several host molecules implicated in TB infections are present in man and nonhuman primates but are not found, or differ fundamentally, in mice and guinea pigs. For example, many primate species, including human, share the presence of functional Mhc-DR, -DQ, and -DP regions (11). The relevance of this structural similarity is reflected in the observation that spec...
We developed a system that allows individual feeding of adult baboons, 8-15 years of age, maintained in an outdoor group social environment. The purpose of the system is to allow careful monitoring and control of individual diet. Baboons were housed in two group cages, 16 females and a single male in one and 12 females and a single male in the other. Baboons exited the group cage once daily and passed along a chute and over a scale into individual cages where they received their individual diets. Food intake was monitored during their 2-hour stay in the individual cages. Baboons rapidly learned to use this system. Food intake and weight were stable within 20 days. Food consumed decreased during the period of sexual receptivity. The maintenance of the group social environment allowed observations on the group's dominance structure and the relationship of dominance to food consumption. Speed of food access in the group cage was related to dominance. Dominance was not related to food consumed in individual cages. The system permits study of many variables related to behavior and food intake while still retaining critical social interactions.
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