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Brasky, K.

Publications and source records attributed to Brasky, K..

3 recordsLinked to original sources

Validation of Body Condition Scoring as a Screening Test for Low Body Condition and Obesity in Common Marmosets (Callithrix jacchus)

Assessing body weight is common practice for monitoring health in common marmosets (Callithrix jacchus). Body composition analysis via quantitative magnetic resonance (QMR) is a more in-depth assessment allowing measurements of lean and fat mass, but it is expensive and remains unavailable to most. Alternatively, body condition scoring (BCS) is an instrument-free method for visually inspecting and palpating lean and fat tissue. Animals are rated for lean and fat mass abundance, using an ordinal scale with species-specific descriptions as reference. However, modified BCS systems developed for other species are being used, because no BCS system has been fully validated for marmosets. The accuracy of BCS in identifying marmosets with poor body condition or obesity remains unknown. We assessed an adapted BCS for marmosets (n=68, 2-16 years). Objectives were to 1) determine whether BCS predicts body weight and body composition, and 2) evaluate the performance of BCS as a screening test for low body condition and obesity in marmosets, in comparison to QMR body composition analysis. BCS predicted body weight and body composition (F(15, 166)=7.51, Wilks {Lambda}=0.240, p<0.001), and was better at predicting low lean mass and obesity, than at predicting low adiposity. Marmosets with low BCS had higher odds of low lean mass (B=3.37, (95% CI, 0.95-5.78), OR=29.0, p=0.006). Marmosets with excessively high BCS had higher odds of obesity (B=2.72, (95% CI, 1.07-4.38), OR=15.23, p=0.001). The accuracy of BCS suggests it can serve as an instrument-free method to screen for low body condition (79.4%-91.2%) and obesity (77.9%) in marmosets. Research highlightsO_LIWe evaluated body condition scoring (BCS) as a screening tool for detecting low body condition and obesity in marmosets by comparing it to diagnoses based on quantitative magnetic resonance, the gold-standard method for body composition analysis. C_LIO_LIBCS was more accurate at detecting low lean mass and obesity than low adiposity, with marmosets having low BCS showing higher odds of low lean mass and those with excessively high BCS having higher odds of obesity. C_LIO_LIResults suggest that BCS can serve as an instrument-free method to screen for low body condition and obesity in marmosets, enabling early detection of health decline and guiding the need for further diagnostic testing and treatment. C_LI

physiology↗

A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD up, two-RBD down state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFN{gamma}+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728).

immunology↗

Subclinical infection of macaques and baboons with a baboon simartevirus

Simarteviruses (Arteriviridae: Simartevirus) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simartevirus pathogenesis by infecting olive baboons (n=4) and rhesus macaques (n=4) with the simartevirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1x107 and 1x108 vRNA copies/ml at 3-10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1x106 and 1x107 vRNA copies/ml for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simartevirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies.\n\nOne Sentence SummarySimartevirus infection has multiple disease manifestations following cross-species transmission.\n\nAccessible Summary/ImportanceSimarteviruses are known to infect African monkeys, such as olive baboons, without causing overt disease. In contrast, accidental infection of Asian monkeys, such as rhesus monkeys, has resulted in severe and often fatal disease. We used a simartevirus found circulating among captive olive baboons (Southwest baboon virus 1; SWBV-1) to experimentally infect both olive baboons and rhesus monkeys to model infection with the same virus in both natural and non-natural hosts. Surprisingly, neither baboons nor macaques displayed any laboratory abnormalities or signs of disease over the course of infection, despite robust SWBV-1 replication. In the accompanying study by Cornish et al., a similar experimental approach was undertaken: African patas monkeys and rhesus monkeys were infected with the simartevirus simian hemorrhagic fever virus (SHFV). In contrast to our study, SHFV caused disease in both of these hosts, albeit with much more severe disease developing in the macaques. Interestingly, we observed similar levels of immune cell activation in simartevirus-infected animals across both studies, suggesting that finer nuances of the host response, and perhaps properties of each individual simartevirus, may influences pathogenicity of these viruses in primates. Taken together, our collective findings highlight the wide clinical spectrum of simartevirus infection, ranging from highly-lethal hemorrhagic disease to persistent infection without any overt signs of disease, even in non-natural primate hosts.

microbiology↗