Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
assessing antigen-specific cellular immune responses upon hiv /siv plasmid dna vaccination in the nonhuman primate model.reliable detection and quantification of antigen-specific t cells are critical for assessing the immunogenicity of vaccine candidates. in this chapter, we describe the use of elispot and flow cytometry-based assays for efficient detection, mapping, and functional characterization of memory t lymphocytes in different tissues of rhesus macaques immunized with plasmid dna. flow cytometric assays provide a large amount of information, both phenotypic and functional, about individual cells, while the ...202132827134
delay-dependent cholinergic modulation of visual short-term memory in rhesus macaques.cholinergic neuromodulation is known to play a key role in visual working memory (vwm) - keeping relevant stimulus representations available for cognitive processes for short time periods (up to a few minutes). despite the growing body of evidence on how the neural and cognitive mechanisms of vwm dynamically change over retention time, there is mixed evidence available on cholinergic effects as a function of vwm delay period in non-human primates. using the delayed matching to sample vwm task in ...202132891649
prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored covid-19 vaccine candidates.abstractcovid-19 vaccines are being developed urgently worldwide. here, we constructed two adenovirus vectored covid-19 vaccine candidates of sad23l-ncov-s and ad49l-ncov-s carrying the full-length gene of sars-cov-2 spike protein. the immunogenicity of two vaccines was individually evaluated in mice. specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. furthermore, five rhesus macaques were primed with 5 × 109 pfu sad23 ...202133993845
low-dose ad26.cov2.s protection against sars-cov-2 challenge in rhesus macaques.we previously reported that a single immunization with an adenovirus serotype 26 (ad26)-vector-based vaccine expressing an optimized sars-cov-2 spike (ad26.cov2.s) protected rhesus macaques against sars-cov-2 challenge. to evaluate reduced doses of ad26.cov2.s, 30 rhesus macaques were immunized once with 1 × 1011, 5 × 1010, 1.125 × 1010, or 2 × 109 viral particles (vp) ad26.cov2.s or sham and were challenged with sars-cov-2. vaccine doses as low as 2 × 109 vp provided robust protection in bronch ...202134133941
low-dose ad26.cov2.s protection against sars-cov-2 challenge in rhesus macaques.we previously reported that a single immunization with an adenovirus serotype 26 (ad26) vector-based vaccine expressing an optimized sars-cov-2 spike (ad26.cov2.s) protected rhesus macaques against sars-cov-2 challenge. in this study, we evaluated the immunogenicity and protective efficacy of reduced doses of ad26.cov2.s. 30 rhesus macaques were immunized once with 1×10 11 , 5×10 10 , 1.125×10 10 , or 2×10 9 vp ad26.cov2.s or sham and were challenged with sars-cov-2 by the intranasal and intratr ...202133532782
evaluating angiotensin-converting enzyme 2-mediated sars-cov-2 entry across species.the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ace2), the primary entry receptor for sars-cov-2, is a key determinant of the range of hosts that can be infected by the virus. however, the mechanisms underpinning ace2-mediated viral entry across species remains unclear. using infection assay, we evaluated sars-cov-2 entry mediated by ace2 of 11 different animal species ...202133610551
host- and species-dependent quasispecies divergence of severe acute respiratory syndrome coronavirus-2 in non-human primate models.recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) have been continuously reported worldwide. however, the precise evaluation of sars-cov-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. in this report, we performed deep sequencing for seed virus and sars-cov-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucl ...202134305860
in vitro characterization of fitness and convalescent antibody neutralization of sars-cov-2 cluster 5 variant emerging in mink at danish farms.in addition to humans, severe acute respiratory syndrome coronavirus 2 (sars-cov-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. among these, mink are particularly susceptible. indeed, 10 countries in europe and north america reported sars-cov-2 infection among mink on fur farms. in denmark, sars-cov-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions wi ...202134248922
sars-cov-2 in animals: potential for unknown reservoir hosts and public health implications.severe acute respiratory syndrome coronavirus 2 (sars-cov-2, previously 2019-ncov) is suspected of having originated in 2019 in china from a coronavirus infected bat of the genus rhinolophus. following the initial emergence, possibly facilitated by a mammalian bridge host, sars-cov-2 is currently transmitted across the globe via efficient human-to-human transmission. results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, ...202133892621
the neutralizing antibody, ly-cov555, protects against sars-cov-2 infection in nonhuman primates.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. here, we report that high-throughput microfluidic screening of antigen-specific b cells led to the identification of ly-cov555 (also known as bamlanivimab), a pot ...202133820835
northern pig-tailed macaques ( macaca leonina) infected with sars-cov-2 show rapid viral clearance and persistent immune response.coronavirus disease 2019 (covid-19), which is caused by severe acute respiratory syndrome coronavirus (sars-cov-2), has become an unprecedented global health emergency. at present, sars-cov-2-infected nonhuman primates are considered the gold standard animal model for covid-19 research. here, we showed that northern pig-tailed macaques ( macaca leonina, npms) supported sars-cov-2 replication. furthermore, compared with rhesus macaques, npms showed rapid viral clearance in lung tissues, nose swab ...202133998182
intranasal chadox1 ncov-19/azd1222 vaccination reduces viral shedding after sars-cov-2 d614g challenge in preclinical models.chadox1 ncov-19/azd1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) currently being deployed globally. previous studies in rhesus macaques revealed that intramuscular vaccination with chadox1 ncov-19/azd1222 provided protection against pneumonia but did not reduce shedding of sars-cov-2 from the upper respiratory tract. here, we investigated whether intranasally administered chadox1 ncov-19 reduces detection of virus in nasal swabs aft ...202134315826
recovery from acute sars-cov-2 infection and development of anamnestic immune responses in t cell-depleted rhesus macaques.severe coronavirus disease 2019 (covid-19) has been associated with t cell lymphopenia, but no causal effect of t cell deficiency on disease severity has been established. to investigate the specific role of t cells in recovery from severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections, we studied rhesus macaques that were depleted of either cd4+, cd8+, or both t cell subsets prior to infection. peak virus loads were similar in all groups, but the resolution of virus in the t c ...202134311582
interferon-armed rbd dimer enhances the immunogenicity of rbd for sterilizing immunity against sars-cov-2.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. a major challenge is that the receptor-binding domain (rbd)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. to enhance antigen processing and cross-presentation in draining lymph nodes (dlns), we developed an interferon (ifn)-armed rbd dimerized by an i ...202134267349
a human antibody of potent efficacy against sars-cov-2 in rhesus macaques showed strong blocking activity to b.1.351.severe acute respiratory syndrome coronavirus-2 (sars-cov-2), which causes coronavirus disease-2019 (covid-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hace2) via its spike 1 protein during infection. after the virus sequence was published, we identified two potent antibodies against the sars-cov-2 receptor binding domain (rbd) from antibody libraries using a phage-to-yeast (pty) display platform in only 10 days. our lead antibody jmb2002, now in a phase 1 clinical ...202134097570
a synthetic peptide ctl vaccine targeting nucleocapsid confers protection from sars-cov-2 challenge in rhesus macaques.persistent transmission of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has given rise to a covid-19 pandemic. several vaccines, conceived in 2020, that evoke protective spike antibody responses are being deployed in mass public health vaccination programs. recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.202134070152
compartmental model suggests importance of innate immune response to covid-19 infection in rhesus macaques.the pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has quickly spread worldwide, creating a serious health crisis. the virus is primarily associated with flu-like symptoms but can also lead to severe pathologies and death. we here present an ordinary differential equation model of the intrahost immune response to sars-cov-2 infection, fitted to experimental data gleaned from rhesus macaques. the model is calibrated to data from a nonlethal infection, but the mo ...202134037874
fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.natural antibodies (abs) can target host glycans on the surface of pathogens. we studied the evolution of glycan-reactive b cells of rhesus macaques and humans using glycosylated hiv-1 envelope (env) as a model antigen. 2g12 is a broadly neutralizing ab (bnab) that targets a conserved glycan patch on env of geographically diverse hiv-1 strains using a unique heavy-chain (vh) domain-swapped architecture that results in fragment antigen-binding (fab) dimerization. here, we describe hiv-1 env fab-d ...202134019795
identification of t cell epitopes in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 in rhesus macaques.the t cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (sars-cov-2) vaccine development. the present study was undertaken to determine the t cell epitopes in the spike (s) protein of sars-cov-2 that dominate the t cell responses in sars-cov-2-infected patients. pbmcs from rhesus macaques vaccinated with a dna vaccine encoding the full-length s protein were isolated, and an elispot assay was used to identify the recognized t cell epitopes among a to ...202133980582
structure and function analysis of a potent human neutralizing antibody ca521fala against sars-cov-2.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is the causative agent of the ongoing covid-19 pandemic, which has resulted in more than two million deaths at 2021 february . there is currently no approved therapeutics for treating covid-19. the sars-cov-2 spike protein is considered a key therapeutic target by many researchers. here we describe the identification of several monoclonal antibodies that target sars-cov-2 spike protein. one human antibody, ca521fala, demonstrated neutr ...202133893388
intradermal delivery of a synthetic dna vaccine protects macaques from middle east respiratory syndrome coronavirus.emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), and severe acute respiratory syndrome coronavirus 2 (sars-cov-2), have been associated with human-to-human transmission and significant morbidity and mortality. here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic dna vaccine candidate encoding a full-length mers-cov spike (s) p ...202133886507
sars-cov-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses.the outbreak and spread of sars-cov-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. the spike glycoprotein of sars-cov-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. here, we show that adjuvanted protein immunization with soluble sars-cov-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, wit ...202133842900
a single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against sars-cov-2 infection in rhesus macaques.the deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (covid-19) pandemic. we recently described the protective activity of an intranasally administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (s) protein (chad-sars-cov-2-s [chimpanzee adenovirus-severe acute respiratory syndrome-coronavirus-2-s]) in the upper and lower respiratory tracts of mice expressing the human angiotensin-convertin ...202133754147
lack of molecular mimicry between nonhuman primates and infectious pathogens: the possible genetic bases.recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. to acquire more data on the issue, analyses here have been expanded to ebola virus, francisella tularensis , human immunode ...202133748822
a modified vaccinia ankara vector-based vaccine protects macaques from sars-cov-2 infection, immune pathology, and dysfunction in the lungs.a combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic. here, we show that modified vaccinia ankara (mva) vectors expressing membrane-anchored pre-fusion stabilized spike (mva/s) but not secreted s1 induced strong neutralizing antibody responses against sars-cov-2 in mice. in macaques, the mva/s vaccination induced strong neutralizing antibodies and cd8+ t cell responses, and conferred protection ...202133631118
suggestions on cleavage embryo and blastocyst vitrification/transfer based on expression profile of ace2 and tmprss2 in current covid-19 pandemic.an outbreak of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is leading to an unprecedented worldwide health crisis. sars-cov-2 cell entry depends on ace2 and tmprss2. our objectives are to analysis the expression profile of ace2 and tmprss2 in human spermatogenic cells, follicle cells, and preimplantation embryos, thereby providing mechanistic insights into viral entry and viral impact on reproduction. we found that ace2 is mainly expressed during gametogenesis in spermatogonia a ...202133624358
the dynamic expression of potential mediators of severe acute respiratory syndrome coronavirus 2 cellular entry in fetal, neonatal, and adult rhesus monkeys.the coronavirus disease 2019 (covid-19) pandemic, induced by the pathogenic severe acute respiratory syndrome coronavirus 2 (sars-cov-2), has spread rapidly all over the world. there is considerable variability among neonates, children, and adults in the incidence of infection and severe disease following exposure to sars-cov-2. in our study, we analyzed the transcriptome data of primate animal model of rhesus monkeys to evaluate the expression levels of possible sars-cov-2 receptors and proteas ...202133537060
rapid protection from covid-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine.the ongoing pandemic of coronavirus disease 2019 (covid-19) continues to exert a significant burden on health care systems worldwide. with limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (sars-cov-2). recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against sars-cov-2. here, ...202133501447
a therapeutic neutralizing antibody targeting receptor binding domain of sars-cov-2 spike protein.vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). here, we screen human monoclonal antibodies (mab) targeting the receptor binding domain (rbd) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. the ct-p59 mab potently neutralizes sars-cov-2 isolates including the d614g variant without antibody-dependent enhancement effect. complex cryst ...202133436577
coronavirus-specific antibody cross reactivity in rhesus macaques following sars-cov-2 vaccination and infection.vaccines are being rapidly developed with the goal of ending the sars-cov-2 pandemic. however, the extent to which sars-cov-2 vaccination induces serum responses that cross-react with other coronaviruses remains poorly studied. here we define serum profiles in rhesus macaques after vaccination with dna or ad26 based vaccines expressing sars-cov-2 spike protein followed by sars-cov-2 challenge, or sars-cov-2 infection alone. analysis of serum responses showed robust reactivity to the sars-cov-2 f ...202133692201
caco-2 cells: a continuous cell line with sensitive and broad-spectrum utility for respiratory virus culture.primary rhesus monkey kidney cells (rhmk) can be used for the detection of respiratory viruses, including influenza and parainfluenza. the human colon adeno-carcinoma cell line, caco-2, has been previously used for the growth of multiple influenza viruses, including seasonal, novel and avian lineages.202133676967
previously published ethno-pharmacological reports reveal the potentiality of plants and plant-derived products used as traditional home remedies by bangladeshi covid-19 patients to combat sars-cov-2.several plants have traditionally been used since antiquity to treat various gastroenteritis and respiratory symptoms similar to covid-19 outcomes. the common symptoms of covid-19 include fever or chills, cold, cough, flu, headache, diarrhoea, tiredness/fatigue, sore throat, loss of taste or smell, asthma, shortness of breath, or difficulty breathing, etc. this study aims to find out the plants and plant-derived products which are being used by the covid-19 infected patients in bangladesh and ho ...202134305428
development of a coronavirus disease 2019 nonhuman primate model using airborne exposure.airborne transmission is predicted to be a prevalent route of human exposure with sars-cov-2. aside from african green monkeys, nonhuman primate models that replicate airborne transmission of sars-cov-2 have not been investigated. a comparative evaluation of covid-19 in african green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to sars-cov-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations betw ...202133529233
myeloid cell interferon responses correlate with clearance of sars-cov-2.the emergence of mutant sars-cov-2 strains associated with an increased risk of covid-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. while studies have reported immune profiling using single cell rna sequencing in terminal human covid-19 patients, performing longitudinal immune cell dynamics in humans is challenging. macaques are a suitable model of sars-cov-2 infection. we performed longitudinal single-cell rna sequencing of b ...202134282414
single-dose immunization with a chimpanzee adenovirus-based vaccine induces sustained and protective immunity against sars-cov-2 infection.the development of a safe and effective vaccine against sars-cov-2, the causative agent of pandemic coronavirus disease-2019 (covid-19), is a global priority. here, we aim to develop novel sars-cov-2 vaccines based on a derivative of less commonly used rare adenovirus serotype adc68 vector. three vaccine candidates were constructed expressing either the full-length spike (adc68-19s) or receptor-binding domain (rbd) with two different signal sequences (adc68-19rbd and adc68-19rbds). single-dose i ...202134262569
one or two dose regimen of the sars-cov-2 synthetic dna vaccine ino-4800 protects against respiratory tract disease burden in nonhuman primate challenge model.safe and effective vaccines will provide essential medical countermeasures to tackle the covid-19 pandemic. here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of ino-4800, a synthetic dna vaccine candidate encoding the sars-cov-2 spike protein in the rhesus macaque model. single and 2 dose vaccination regimens were evaluated. vaccination induced both binding and neutralizing antibodies, along with ifn-γ-producing t cells against sars-cov-2. upon administration ...202134253420
why remdesivir failed: preclinical assumptions overestimate the clinical efficacy of remdesivir for covid-19 and ebola.remdesivir is a nucleoside monophosphoramidate prodrug that has been fda-approved for covid-19. however, the clinical efficacy of remdesivir for covid-19 remains contentious, as several trials have not found statistically significant differences in either time to clinical improvement or mortality between remdesivir-treated and control groups. similarly, the inability for remdesivir to provide a clinically significant benefit above other investigational agents in patients with ebola contrasts wit ...202134252308
transmission of infectious viruses in the natural setting at human-animal interface.most viral pathogens causing epidemics and pandemics are zoonotic, emerging from wildlife reservoirs like sars cov2 causing the global covid-19 pandemic, although animal origin of this virus remains a mystery. cross-species transmission of pathogens from animals to humans is known as zoonosis. however, pathogens are also transmitted from humans to animals in regions where there is a close interaction between animals and humans by 'reverse transmission' (anthroponosis). molecular evidence for the ...202134250513
early treatment with a combination of two potent neutralizing antibodies improves clinical outcomes and reduces virus replication and lung inflammation in sars-cov-2 infected macaques.there is an urgent need for effective therapeutic interventions against sars-cov-2, including new variants that continue to arise. neutralizing monoclonal antibodies have shown promise in clinical studies. we investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, c135-ls and c144-ls that carry half-life extension mutations, in the rhesus macaque model of covid-19. twelve young adult macaques (three groups of four animals) were inoculated intranasally and intr ...202134228761
a recombinant receptor-binding domain in trimeric form generates protective immunity against sars-cov-2 infection in nonhuman primates.a safe and effective vaccine is critical to combat the covid-19 pandemic. here, we developed a trimeric sars-cov-2 receptor-binding domain (rbd) subunit vaccine candidate that simulates the natural structure of the spike (s) trimer glycoprotein. immunization with the rbd trimer-induced robust humoral and cellular immune responses, and a high level of neutralizing antibodies was maintained for at least 4.5 months. moreover, the antibodies that were produced in response to the vaccine effectively ...202134179862
protective efficacy of ad26.cov2.s against sars-cov-2 b.1.351 in macaques.the emergence of sars-cov-2 variants that partially evade neutralizing antibodies poses a threat to the efficacy of current covid-19 vaccines1,2. the ad26.cov2.s vaccine expresses a stabilized spike protein from the wa1/2020 strain of sars-cov-2, and has recently demonstrated protective efficacy against symptomatic covid-19 in humans in several geographical regions-including in south africa, where 95% of sequenced viruses in cases of covid-19 were the b.1.351 variant3. here we show that ad26.cov ...202134161961
the fc-mediated effector functions of a potent sars-cov-2 neutralizing antibody, sc31, isolated from an early convalescent covid-19 patient, are essential for the optimal therapeutic efficacy of the antibody.although sars-cov-2-neutralizing antibodies are promising therapeutics against covid-19, little is known about their mechanism(s) of action or effective dosing windows. we report the generation and development of sc31, a potent sars-cov-2 neutralizing antibody, isolated from a convalescent patient. antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the sars-cov-2 spike protein. sc31 exhibited potent anti-sars-cov-2 activities in multiple animal models. i ...202134161386
sars-cov-2 vaccines elicit durable immune responses in infant rhesus macaques.the inclusion of infants in the sars-cov-2 vaccine roll-out is important to prevent severe complications of pediatric sars-cov-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. however, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. toward this goal, we assessed the safety and immunogenicity of two sars-cov-2 vaccines. two groups of 8 infant rhesus macaques (r ...202134131024
control theory helps to resolve the measles paradox.measles virus (mv) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. a crucial challenge in studying mv infection is to understand the so-called 'measles paradox'-the progression of the infection to severe immunosuppression before clearance of acute viremia, which is also observed in canine distemper virus (cdv) infection. however, a lack of models that match in vivo data has restricted our understanding of this complex and counter-intuitive phenomeno ...202134007460
a sars-cov-2 neutralizing antibody with extensive spike binding coverage and modified for optimal therapeutic outcomes.covid-19 pandemic caused by sars-cov-2 constitutes a global public health crisis with enormous economic consequences. monoclonal antibodies against sars-cov-2 can provide an important treatment option to fight covid-19, especially for the most vulnerable populations. in this work, potent antibodies binding to sars-cov-2 spike protein were identified from covid-19 convalescent patients. among them, p4a1 interacts directly with and covers majority of the receptor binding motif of the spike recepto ...202133976198
ultrasensitive detection and quantification of viral nucleic acids with raindance droplet digital pcr (ddpcr).sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by sars-cov2, hiv-1, and other viruses. in hiv-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cart) has benefited tremendously from the development of sensitive hiv-1 dna and rna quantitation assays. simian immunodeficiency virus (siv) infection of rhesus ma ...202133957204
self-assembling nanoparticle vaccines displaying the receptor binding domain of sars-cov-2 elicit robust protective immune responses in rhesus monkeys.sars-cov-2 caused the covid-19 pandemic that lasted for more than a year. globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against sars-cov-2 infection. focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a sars-cov-2 spike protein receptor-binding domain (rbd) displayed on self-assembled ferritin nanoparticles. in a 293i cells eukaryot ...202133951913
protection against sars-cov-2 infection by a mucosal vaccine in rhesus macaques.effective sars-cov-2 vaccines are urgently needed. although most vaccine strategies have focused on systemic immunization, here we compared the protective efficacy of 2 adjuvanted subunit vaccines with spike protein s1: an intramuscularly primed/boosted vaccine and an intramuscularly primed/intranasally boosted mucosal vaccine in rhesus macaques. the intramuscular-alum-only vaccine induced robust binding and neutralizing antibody and persistent cellular immunity systemically and mucosally, where ...202133908897
the olfactory route is a potential way for sars-cov-2 to invade the central nervous system of rhesus monkeys.neurological manifestations are frequently reported in the covid-19 patients. neuromechanism of sars-cov-2 remains to be elucidated. in this study, we explored the mechanisms of sars-cov-2 neurotropism via our established non-human primate model of covid-19. in rhesus monkey, sars-cov-2 invades the cns primarily via the olfactory bulb. thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. the infection of sars- ...202133895780
adjuvanting a subunit covid-19 vaccine to induce protective immunity.the development of a portfolio of covid-19 vaccines to vaccinate the global population remains an urgent public health imperative1. here we demonstrate the capacity of a subunit vaccine, comprising the sars-cov-2 spike protein receptor-binding domain displayed on an i53-50 protein nanoparticle scaffold (hereafter designated rbd-np), to stimulate robust and durable neutralizing-antibody responses and protection against sars-cov-2 in rhesus macaques. we evaluated five adjuvants including essai o/w ...202133873199
recovery from acute sars-cov-2 infection and development of anamnestic immune responses in t cell-depleted rhesus macaques.severe covid-19 has been associated with t cell lymphopenia 1,2, but no causal effect of t cell deficiency on disease severity has been established. to investigate the specific role of t cells in recovery from sars-cov-2 infections we studied rhesus macaques that were depleted of either cd4+, cd8+ or both t cell subsets prior to infection. peak virus loads were similar in all groups, but the resolution of virus in the t cell-depleted animals was slightly delayed compared to controls. the t cell- ...202133821272
sars-cov-2 infection challenge experiments in nonhuman primates: an ethical perspective.the covid-19 pandemic has stimulated massive investment in biomedical research with the aims of understanding the disease and developing effective vaccine and therapeutic interventions. what role should animal research play in this scientific endeavor? both the urgency to evaluate candidate interventions for human use and growing societal concern about ethical treatment of (nonhuman) animals put into question the justifiability of animal research as a precursor to clinical trials. yet forgoing a ...202133786589
integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in covid-19 patients with therapeutic implications.cytokine release syndrome (crs) is a major cause of the multi-organ injury and fatal outcome induced by sars-cov-2 infection in severe covid-19 patients. metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in covid-19 patients. here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and sever ...202133712622
ifn signaling and neutrophil degranulation transcriptional signatures are induced during sars-cov-2 infection.sars-cov-2 virus has infected more than 92 million people worldwide resulting in the coronavirus disease 2019 (covid-19). using a rhesus macaque model of sars-cov-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. genes associated with interferon (ifn) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen forma ...202133674719
immunogenicity and protective efficacy of inactivated sars-cov-2 vaccine candidate, bbv152 in rhesus macaques.the covid-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. safe and effective vaccines are needed to overcome this crisis. here, we develop and assess the protective efficacy and immunogenicity of an inactivated sars-cov-2 vaccine in rhesus macaques. twenty macaques were divided into four groups of five animals each. one group was administered a placebo, while three groups were immunized with three different vaccine candidates ...202133654090
s-trimer, a covid-19 subunit vaccine candidate, induces protective immunity in nonhuman primates.sars-cov-2 is the underlying cause for the covid-19 pandemic. like most enveloped rna viruses, sars-cov-2 uses a homotrimeric surface antigen to gain entry into host cells. here we describe s-trimer, a native-like trimeric subunit vaccine candidate for covid-19 based on trimer-tag technology. immunization of s-trimer with either as03 (oil-in-water emulsion) or cpg 1018 (tlr9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and th1-biased cellular immune responses in ani ...202133649323
differential efficiencies to neutralize the novel mutants b.1.1.7 and 501y.v2 by collected sera from convalescent covid-19 patients and rbd nanoparticle-vaccinated rhesus macaques. 202133580167
a novel dna and protein combination covid-19 vaccine formulation provides full protection against sars-cov-2 in rhesus macaques.the current study aims to develop a safe and highly immunogenic covid-19 vaccine. the novel combination of a dna vaccine encoding the full-length spike (s) protein of sars-cov-2 and a recombinant s1 protein vaccine induced high level neutralizing antibody and t cell immune responses in both small and large animal models. more significantly, the co-delivery of dna and protein components at the same time elicited full protection against intratracheal challenge of sars-cov-2 viruses in immunized rh ...202133555988
a single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against sars-cov-2 infection in rhesus macaques.the deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (covid-19) pandemic. we recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (s) protein (chad-sars-cov-2-s) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ace2) receptor. here, we show the immunogenicity and protective ...202133532770
bundibugyo ebolavirus survival is associated with early activation of adaptive immunity and reduced myeloid-derived suppressor cell signaling.ebolaviruses bundibugyo virus (bdbv) and ebola virus (ebov) cause fatal hemorrhagic disease in humans and nonhuman primates. while the host response to ebov is well characterized, less is known about bdbv infection. moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. to explore these knowledge gaps, we transcriptionally profiled bdbv-infected rhesus macaques, a disease model that results in incomplete lethality. this approach enabled us to ...202134372693
distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.ebola virus (ebov) is a negative single-stranded rna virus within the filoviridae family and the causative agent of ebola virus disease (evd). nonhuman primates (nhps), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of ebov pathogenesis. however, despite significant genetic similarity (>90%), nhp species display different clinical presentation following ebov infection, notably a ∼1-2 days delay in disease progression. consequentl ...202134112056
identification and characterization of defective viral genomes in ebola virus-infected rhesus macaques.ebola virus (ebov), of the family filoviridae, is an rna virus that can cause a hemorrhagic fever with a high mortality rate. defective viral genomes (dvgs) are truncated genomes that have been observed during multiple rna virus infections, including in vitro ebov infection, and have previously been associated with viral persistence and immunostimulatory activity. as dvgs have been detected in cells persistently infected with ebov, we hypothesized that dvgs may also accumulate during viral repli ...202134160256
development of a well-characterized rhesus macaque model of ebola virus disease for support of product development.ebola virus (ebov) is a negative-sense rna virus that can infect humans and nonhuman primates with severe health consequences. development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. the goal of this study was to further characterize ebov disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. rhesus macaques were intram ...202133652589
functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with hcv envelope glycoproteins.human ighv1-69-encoded broadly neutralizing antibodies (bnabs) that target the hepatitis c virus (hcv) envelope glycoprotein (env) e2 are important for protection against hcv infection. an ighv1-69 ortholog gene, vh1.36, is preferentially used for bnabs isolated from hcv env-immunized rhesus macaques (rms). here, we studied the genetic, structural, and functional properties of vh1.36-encoded bnabs generated by vaccination, in comparison to ighv1-69-encoded bnabs from hcv patients. global b cell ...202133675683
previous exposure to dengue virus is associated with increased zika virus burden at the maternal-fetal interface in rhesus macaques.concerns have arisen that pre-existing immunity to dengue virus (denv) could enhance zika virus (zikv) disease, due to the homology between zikv and denv and the observation of antibody-dependent enhancement (ade) among denv serotypes. to date, no study has examined the impact of pre-existing denv immunity on zikv pathogenesis during pregnancy in a translational non-human primate model. here we show that macaques with a prior denv-2 exposure had a higher burden of zikv vrna in maternal-fetal int ...202134329306
early embryonic loss following intravaginal zika virus challenge in rhesus macaques.zika virus (zikv) is an arthropod-borne virus (arbovirus) and is primarily transmitted by aedes species mosquitoes; however, zikv can also be sexually transmitted. during the initial epidemic and in places where zikv is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. to examine the potential impact of sexual transmission of zikv on pregnancy outcome, we challenged three rhesus macaques (m ...202134079560
african-lineage zika virus replication dynamics and maternal-fetal interface infection in pregnant rhesus macaques.following the zika virus (zikv) outbreak in the americas, zikv was causally associated with microcephaly and a range of neurological and developmental symptoms, termed congenital zika syndrome (czs). the viruses responsible for this outbreak belonged to the asian lineage of zikv. however, in vitro and in vivo studies assessing the pathogenesis of african-lineage zikv demonstrated that african-lineage isolates often replicated to high titers and caused more-severe pathology than asian-lineage iso ...202134076485
a high throughput reporter virus particle microneutralization assay for quantitation of zika virus neutralizing antibodies in multiple species.zika virus is a flavivirus, transmitted via aedes mosquitos, that causes a range of symptoms including zika congenital syndrome. zika has posed a challenging situation for health, public and economic sectors of affected countries. to quantitate zika virus neutralizing antibody titers in serum samples, we developed a high throughput plate based zika virus reporter virus particle (rvp) assay that uses an infective, non-replicating particle encoding zika virus surface proteins and capsid (cprme) an ...202133891631
zika virus-like particle vaccine protects ag129 mice and rhesus macaques against zika virus.zika virus (zikv), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and guillain-barré syndrome in adults. to date, there are no approved vaccines against zikv infection. various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for zikv.202133711018
two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against zika virus infection in rhesus macaques.zika virus (zikv) infection has caused major public health problems recently. to develop subunit vaccines for zikv, we have previously constructed recombinant zikv envelope protein domain iii (ediii), and the entire ectodomain (e80, which comprises edi, edii and ediii), as vaccine candidates and showed both of them being immunogenic and protective in murine models. in this follow-up study, we compared these vaccine candidates in non-human primates. both of them elicited neutralizing antibody res ...202133451779
clinical and preclinical evidence for adverse neurodevelopment after postnatal zika virus infection.although the zika virus (zikv) typically causes mild or no symptoms in adults, during the 2015-2016 outbreak, zikv infection in pregnancy resulted in a spectrum of diseases in infants, including birth defects and neurodevelopmental disorders identified in childhood. while intense clinical and basic science research has focused on the neurodevelopmental outcomes of prenatal zikv infection, less is known about the consequences of infection during early life. considering the neurotropism of zikv an ...202133445671
transcriptional signatures of zika virus infection in astrocytes.astrocytes are an early and important target of zika virus (zikv) infection in the developing brain, but the impacts of infection on astrocyte function remain controversial. given that nonhuman primate (nhp) models of zikv infection replicate aspects of neurologic disease seen in human infections, we cultured primary astrocytes from the brain tissue of infant rhesus macaques and then infected the cells with asian or african lineage zikv to identify transcriptional patterns associated with infect ...202133405202
fetal rhesus monkey first trimester zika virus infection impacts cortical development in the second and third trimesters.zika virus is a teratogen similar to other neurotropic viruses, notably cytomegalovirus and rubella. the goal of these studies was to address the direct impact of zika virus on fetal development by inoculating early gestation fetal rhesus monkeys using an ultrasound-guided approach (intraperitoneal vs. intraventricular). growth and development were monitored across gestation, maternal samples collected, and fetal tissues obtained in the second trimester or near term. although normal growth and a ...202133341889
potent bispecific neutralizing antibody targeting glycoprotein b and the gh/gl/pul128/130/131 complex of human cytomegalovirus.human cytomegalovirus (hcmv) is a ubiquitous pathogen that can cause developmental disorders following congenital infection and life-threatening complications among transplant patients. potent neutralizing monoclonal antibodies (mabs) are promising drug candidates against hcmv infection. hcmv can infect a broad range of cell types. therefore, single neutralizing antibodies targeting one hcmv glycoprotein often lack either potency or broad cell-type coverage. we previously characterized two human ...202133361306
intratracheal inoculation of human varicella zoster virus (vzv; mav strain) vaccine successfully induced vzv igg antibodies in rhesus monkeys.the objective of this study was to investigate whether the use of live attenuated varicella zoster virus (vzv) mav vaccination can efficiently induce vzv antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (svv) reactivation in animals immunosuppressed for transplantation studies.202134022964
study of the teratogenicity of the vaccine strain of the rubella virus «orlov-v» (matonaviridae: rubivirus: rubella virus) in experience on rhesus macaques.rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. as a result, the control of the loss of teratogenicity inherent in «wild-type» virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.the purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «orlov-v» in the experiment on rhesus macaques.202133533577
respiratory tract explant infection dynamics of influenza a virus in california sea lions, northern elephant seals, and rhesus macaques.to understand susceptibility of wild california sea lions and northern elephant seals to influenza a virus (iav), we developed an ex vivo respiratory explant model and used it to compare infection kinetics for multiple iav subtypes. we first established the approach using explants from colonized rhesus macaques, a model for human iav. trachea, bronchi, and lungs from 11 california sea lions, 2 northern elephant seals, and 10 rhesus macaques were inoculated within 24 h postmortem with 6 strains r ...202134037419
host-cell dependent role of phosphorylated keratin 8 during influenza a/nws/33 virus (h1n1) infection in mammalian cells.in this study, we investigated the involvement of keratin 8 during human influenza a/nws/33 virus (h1n1) infection in semi-permissive rhesus monkey-kidney (llc-mk2) and permissive human type ii alveolar epithelial (a549) cells. in a549 cells, keratin 8 showed major expression and phosphorylation levels. influenza a/nws/33 virus was able to subvert keratin 8 structural organization at late stages of infection in both cell models, promoting keratin 8 phosphorylation in a549 cells at early phases o ...202133556415
development of a simian rna polymerase i promoter-driven reverse genetics for the rescue of recombinant rift valley fever virus from vero cells.rift valley fever (rvf), which has been designated as a priority disease by the world health organization (who), is one of the most pathogenic zoonotic diseases endemic to africa and the arabian peninsula. human vaccine preparation requires the use of appropriate cell substrates to support efficient production of seed vaccine with minimum concerns of tumorigenicity, oncogenicity, or adventitious agents. vero cells, which were derived from the african green monkey kidney, represent one of the few ...202133441343
oral vaccination approaches for anti-shiv immunity.we modified a sabin oral poliovirus vaccine (opv) vector to permit secretion of the antigens of interest with the goal of improving anti-hiv env humoral responses in a shiv mucosal immunization composed of dna and recombinant opvs. we evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in rhesus macaques by two regimens, both involving a prime with a shivbg505 dna construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral ...202134234789
luminal microvesicles uniquely influence translocating bacteria after siv infection.microbial translocation contributes to persistent inflammation in both treated and untreated hiv infection. although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of proteobacteria. we hypothesized that intestinal epithelial microvesicle cargo differs after hiv infection and contributes to biased translocation. we isolated gastrointestinal luminal microvesicles before and after progressive simian immunodeficiency ...202133731830
development and evaluation of a rapid and cost-efficient ngs-based mhc class i genotyping method for macaques by using a prevalent short-read sequencer.rhesus macaque is one of the most widely used primate model animals for immunological research of infectious diseases including human immunodeficiency virus (hiv) infection. it is well known that major histocompatibility complex (mhc) class i genotypes affect the susceptibility and disease progression to simian immunodeficiency virus (siv) in rhesus macaques, which is resembling to hiv in humans. it is required to convincingly determine the mhc genotypes in the immunological investigations, that ...202133447871
monitoring immune activation with whole-body fluorodeoxyglucose-positron-emission tomography in simian immunodeficiency virus-infected rhesus macaques.this study aimed to assess immune activation in tissues by measuring glucose metabolism with 18f-fluorodeoxyglucose (fdg) and investigate the associations of various peripheral markers of disease progression with initiation and interruption of combination antiretroviral therapy in siv-infected rhesus macaques (macaca mulatta). mixed-effect linear models revealed a significant inverse association of peripheral blood cd4+ t cell counts (p < 0.01) and a direct association of plasma viral load (p < ...202134282030
vaccine nanodiscs plus polyiclc elicit robust cd8+ t cell responses in mice and non-human primates.conventional cancer vaccines based on soluble vaccines and traditional adjuvants have produced suboptimal therapeutic efficacy in clinical trials. thus, there is an urgent need for vaccine technologies that can generate potent t cell responses with strong anti-tumor efficacy. we have previously reported the development of synthetic high-density protein (shdl) nanodiscs for efficient lymph node (ln)-targeted co-delivery of antigen peptides and cpg oligonucleotides (a toll-like receptor-9 agonist) ...202134280415
invaplex functions as an intranasal adjuvant for subunit and dna vaccines co-delivered in the nasal cavity of nonhuman primates.development of intranasal vaccines for hiv-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. we have found that an intranasal shigella vaccine (invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and dna vaccines in mice. to determine whether invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (siv) envelope (env) pr ...202134258576
late-phase dominance of a single epitope-specific cd8+ t-cell response in passive neutralizing antibody-infused siv controllers.analysis of the quantity and quality of epitope-specific cd8+ t-cell responses is crucial for understanding the mechanism of hiv/simian immunodeficiency virus (siv) replication control. we have previously shown that acute-phase passive infusion of neutralizing antibodies (nabs) results in augmented broad t-cell responses and robust sivmac239 control in rhesus macaques. analyzing long-term dynamics of cd8+ t-cell responses in these siv controllers provides important insights into designing lastin ...202134224443
neutralizing antibody induction associated with a germline immunoglobulin gene polymorphism in neutralization-resistant sivsme543-3 infection.antibody responses are crucial for the control of virus infection. understanding of the mechanism of antibody induction is important for the development of a vaccine eliciting effective anti-virus antibodies. virus-specific b cell receptor (bcr)/antibody repertoires are different among individuals, but determinants for this difference remain largely unclear. we have recently reported that a germline bcr immunoglobulin (igg) gene polymorphism (vh3.33_et or vh3.33_vi) in rhesus macaques is the det ...202134205728
viremia controls env-specific antibody-secreting cell responses in siv-infected macaques pre- and post-art.to investigate the kinetics of env (gp140)-specific antibody-secreting cells (ascs) during acute and early chronic simian immunodeficiency virus (siv) infection, and prior to and post-antiretroviral therapy (art) in rhesus macaques (rms).202134148985
lack of specific regulatory t cell depletion and cytoreduction associated with extensive toxicity after administration of low and high doses of cyclophosphamide.up to 93% of the human immunodeficiency virus (hiv) latent reservoir comprised defective proviruses, suggesting that a functional cure is possible through the elimination of a small population of cells containing intact virus, instead of the entire reservoir. cyclophosphamide (cy) is an established chemotherapeutic agent for immune cell cancers. in high doses, cy is a nonselective cytoreductor, used in allogeneic stem-cell transplantation, while in a low dose, metronomic schedule, cy selectively ...202133957772
enhanced intestinal tgf-β/smad-dependent signaling in simian immunodeficiency virus infected rhesus macaques.transforming growth factor-β signaling (tgf-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either smad2/3 and smad7 (smad-dependent) or smad-independent signaling pathways under normal conditions. increased production of tgf-β promotes immunosuppression in human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection. however, the cellular source and downstream events of inc ...202133916615
recombinant herpesvirus vectors: durable immune responses and durable protection against simian immunodeficiency virus sivmac239 acquisition.a prophylactic vaccine that confers durable protection against human immunodeficiency virus (hiv) would provide a valuable tool to prevent new hiv/aids cases. as herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver hiv antigens may facilitate the induction of long-term anti-hiv immunity. we previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rrrv) expressing a replication-inco ...202133910957
human immunodeficiency virus-1/simian immunodeficiency virus infection induces opening of pannexin-1 channels resulting in neuronal synaptic compromise: a novel therapeutic opportunity to prevent neurohiv.in healthy conditions, pannexin-1 (panx-1) channels are in a close state, but in several pathological conditions, including human immunodeficiency virus-1 (hiv) and neurohiv, the channel becomes open. however, the mechanism or contribution of panx-1 channels to the hiv pathogenesis and neurohiv is unknown. to determine the contribution of panx-1 channels to the pathogenesis of neurohiv, we used a well-established model of simian immunodeficiency virus (siv) infection in macaques (macaca mulatta) ...202133899944
antiretroviral therapy administration reduces neuroinflammation without restoring brain-derived neurotrophic factor signaling in alcohol-administered simian immunodeficiency virus-infected macaques.the present study examined interactions between simian immunodeficiency virus (siv), chronic binge alcohol (cba), and antiretroviral therapy (art) on growth factor signaling, neuroinflammatory markers, viral loads (vl), and cd4+ cell counts.202133813553
dimethyl fumarate, an approved multiple sclerosis treatment, reduces brain oxidative stress in siv-infected rhesus macaques: potential therapeutic repurposing for hiv neuroprotection.dimethyl fumarate (dmf), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. we hypothesized that dmf administration to simian immunodeficiency virus (siv)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. nine siv-infected, cd8+-t-lymphocyte-depleted rhesus macaques were studied. five received oral dmf ...202133803289
non-neutralizing antibodies may contribute to suppression of sivmac239 viremia in indian rhesus macaques.the antiviral properties of broadly neutralizing antibodies against hiv are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. while current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (siv) and hiv, the ability of these responses to restrict lentivirus transmission and replication remains controversial. here, we investigated the antiviral properties of non-neutralizing antibodie ...202133796119
chronic opioid administration is associated with prevotella-dominated dysbiosis in sivmac251 infected, cart-treated macaques.people living with the human immunodeficiency virus (hiv) have an elevated risk of opioid misuse due to both prescriptions for hiv-associated chronic pain and because injection drug use remains a primary mode of hiv transmission. hiv pathogenesis is characterized by chronic immune activation and microbial dysbiosis, and translocation across the gut barrier exacerbating inflammation. despite the high rate of co-occurrence, little is known about the microbiome during chronic opioid use in the cont ...202133788119
hla-e-restricted, gag-specific cd8+ t cells can suppress hiv-1 infection, offering vaccine opportunities.human leukocyte antigen-e (hla-e) normally presents an hla class ia signal peptide to the nkg2a/c-cd94 regulatory receptors on natural killer (nk) cells and t cell subsets. rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (siv) vaccine generated mamu-e (hla-e homolog)-restricted t cell responses that mediated post-challenge siv replication arrest in >50% of animals. however, hiv-1-specific, hla-e-restricted t cells have not been observed in hiv-1-infected i ...202133766848
comparison of predictors for terminal disease progression in simian immunodeficiency virus/simian-hiv-infected rhesus macaques.cd4+ t-cell decline and increasing virus levels are considered hallmarks of hiv/aids pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by simian immunodeficiency virus (siv) infection associated with increased monocyte turnover also appear to impact pathogenesis. it remains unclear, however, which factors best predict onset of terminal disease progression and survival time. the objective of this study, therefore, was to directly compare these co-va ...202133710021
two human monoclonal hla-reactive antibodies cross-react with mamu-b*008, a rhesus macaque mhc allotype associated with control of simian immunodeficiency virus replication.mhc class i molecules play an important role in adaptive immune responses against intracellular pathogens. these molecules are highly polymorphic, and many allotypes have been characterized. in a transplantation setting, a mismatch between mhc allotypes may initiate an alloimmune response. rhesus macaques (macaca mulatta, mamu) are valuable as a preclinical model species in transplantation research as well as to evaluate the safety and efficacy of vaccine candidates. in both lines of research, t ...202133692147
development of a reverse transcription droplet digital pcr (rt-ddpcr) assay for sensitive detection of simian immunodeficiency virus (siv).simian immunodeficiency virus (siv)-infected rhesus macaques constitute an excellent model of human hiv infection. sensitive detection of siv rna in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in hiv cure research.202133588884
Refresh
firstprev
12345678910...
nextlast
Displaying items 1 - 100 of 30434