Biology subjects

Slifka, M. K.

Publications and source records attributed to Slifka, M. K..

4 recordsLinked to original sources

bioRxiv2025

Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates

Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

pathology↗

bioRxiv2022

Therapeutic neutralizing monoclonal antibody administration protects against lethal viscerotropic Yellow Fever infection

Few countermeasures to treat Yellow Fever virus (YFV) infection are under development, because vaccines have helped to limit new infections. Unfortunately, vaccine hesitancy, supply deficits, and a paucity of therapeutic options have left individuals at risk. Here, we tested potent YFV-specific neutralizing monoclonal antibodies in rodents and non-human primates. We administered antibodies during acute pathogenic YFV infection and demonstrate that we can prevent severe disease and death. Given the severity of YFV-induced disease, our results show that these antibodies could be effective in saving lives and fill a much-needed void in managing Yellow Fever cases during outbreaks around the world. One Sentence SummaryTherapeutic monoclonal antibodies prevent death from YFV infection.

immunology↗

bioRxiv2022

Taxonomic and functional shifts in the perinatal gut microbiome of rhesus macaques

Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables such as diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the perinatal and post-partum periods in 25 rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched during pregnancy while Treponema, Lachnospiraceae, and Methanosphaera were more abundant post-partum. Functionally, pregnancy was associated with increased abundance in the pathway to produce the beneficial short chain fatty acid (SCFA), butyrate, while pathways associated with starch degradation and folate transformation were more abundant postpartum. These data demonstrate dramatic changes in the maternal gut even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy.

microbiology↗

bioRxiv2020

Longitudinal profiling of the macaque vaginal microbiome reveals similarities to diverse human vaginal communities: implications for use as a pre-clinical model for bacterial vaginosis

The vaginal microbiota plays an important role in womens reproductive and urogenital health. Disturbances in this microbial community can lead to several adverse outcomes including pelvic inflammatory disease, bacterial vaginosis (BV) as well as increased susceptibility to sexually transmitted infections, miscarriage, and pre-term births. It is now well accepted that while the microbiome of healthy women in the developed world is dominated by Lactobacillus species, vaginal communities in asymptomatic women, especially those in the developing world, can be comprised of a diverse set of micro-organisms. The presence of a diverse vaginal microbiome has been associated with increased susceptibility to HIV infection but their implications for womens health remain poorly understood. Rhesus macaques are an excellent translational animal model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from 16 reproductive age female rhesus macaques. Many animals showed hallmarks of BV, including Nugent scores above 7 and high vaginal pH. At both the taxonomic and functional level, the rhesus macaque vaginal microbiome was most similar to that of women who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Specifically, rhesus macaque vaginal microbiomes harbored a diverse set of anaerobic gram-negative bacteria, including; Snethia, Prevotella, Porphyromonas, and Mobilluncus. Interestingly, some animals were transiently colonized by Lactobacillus and some with Gardnerella. Our in-depth and comprehensive analysis highlights the importance of the model to test interventions for manipulating the vaginal microbiome. IMPORTANCEIt is widely accepted that the "healthy" vaginal microbiome of the majority of women in the developed world is dominated by Lactobacillus species. However, in the developing world, a majority of women are colonized by diverse microbial communities, typically associated with bacterial vaginosis, but remain asymptomatic. Many questions remain about the drivers of this disparity and potential interventions to alter the vaginal microbiome. Rhesus macaques provide an excellent translational model due to significant physiological and genetic homology with humans. In this study, we performed a longitudinal analysis of clinical and microbiome data from a large cohort of reproductive age rhesus macaques. At the taxonomic, genomic, and functional level, the rhesus macaque vaginal microbiome was most similar to that of humans who harbor a diverse vaginal community associated with asymptomatic/symptomatic bacterial vaginosis. Our in-depth and comprehensive analysis highlights the utility of macaques to test interventions for manipulating the vaginal microbiome.

microbiology↗