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Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates.

The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared …

Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, Reverse Transcriptase Simian-Human Immunodeficiency Virus RNA, and Fibrosis in the Spleens of Nonhuman Primates.

Although current antiretroviral therapy (ART) has increased life expectancy, a cure for human immunodeficiency virus (HIV) remains elusive due to the persistence of the virus in tissue reservoirs. In the present study, we sought to elucidate the relationship between antiretrovirals (ARVs) and viral expression in the spleen. We performed mass spectrometry imaging (MSI) of 6 different ARVs, RNAscope in situ hybridization of viral RNA, and immunohistochemistry of three different fibrosis markers in the spleens of 8 uninfected and 10 reverse transcriptase simian-human immunodeficiency virus (RT-SH

Ebola-GP DNA Prime rAd5-GP Boost: Influence of Prime Frequency and Prime/Boost Time Interval on the Immune Response in Non-human Primates.

Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ+ TNFα+ double positive CD8+ T-cells. In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-…

Frozen blood clots can be used for the diagnosis of distinct Plasmodium species in man and non-human primates from the Brazilian Atlantic Forest.

BACKGROUND: Zoonotic infections with epidemic potential, as non-human primate malaria and yellow fever (YF), can overlap geographically. Optimizing a small blood sample for diagnosis and surveillance is of great importance. Blood are routinely collected for YF diagnosis and blood clots usually discarded after serum obtention. Aiming to take sample advantage, the sensitivity of a PCR using extracted DNA from long-term frozen clots from human and non-human primates for detection of Plasmodium spp. in low parasitaemia conditions was assayed. RESULTS: Malaria diagnosis with DNA extracted from blo…

Comparison of Aerosol- and Percutaneous-acquired Venezuelan Equine Encephalitis in Humans and Nonhuman Primates for Suitability in Predicting Clinical Efficacy under the Animal Rule.

Licensure of medical countermeasure vaccines to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires the use of the Animal Rule to assess vaccine efficacy, because human studies are not feasible or ethical. We therefore performed a retrospective study of VEE cases that occurred in at-risk laboratory workers and support personnel during the United States Biowarfare Program (1943-1969) to better define percutaneous- and aerosol-acquired VEE in humans and to compare these results with those described for the NHP model (in which high-dose aerosol VEEV challenge led to m

Development of dose-response models of Creutzfeldt-Jakob disease infection in nonhuman primates for assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease.

UNLABELLED: Estimates for the risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion have relied largely on data from rodent experiments, but the relationship between dose (amount of infected blood) and response (vCJD infection) has never been well quantified. The goal of this study was to develop a dose-response model based on nonhuman primate data to better estimate the likelihood of transfusion-transmitted vCJD (TTvCJD) in humans. Our model used dose-response data from nonhuman primates inoculated intracerebrally (i.c.) with brain tissues of patients with sporad…

Evidence for simian immunodeficiency virus-specific IgM and IgG response in peripheral blood mononuclear cells of serum enzyme-linked immunosorbent assay-negative nonhuman primates.

In vitro polyclonal activation of peripheral blood mononuclear cells (PBMCs) from 70% of the simian immunodeficiency virus (SIV) serum enzyme-linked, immunosorbent assay (ELISA)-negative sooty mangabeys leads to synthesis and release of low but significant and reproducible levels of SIV-reactive antibodies, as determined by ELISA and Western blot analysis. The predominant isotype of SIV-reactive antibodies in the pokeweed mitogen (PWM) supernatant fluids from serum ELISA-negative mangabeys is IgM, whereas the predominant isotype of SIV-reactive antibodies in seropositive mangabeys is IgG. Depl

Oral administration of cyclosporin does not prevent expansion of antigen-specific, gut-associated, and spleen lymphocyte populations during Chlamydia trachomatis proctitis in nonhuman primates.

To study the effects of oral cyclosporin (CsA) administration on immune responses in the gastrointestinal tract, humoral and cellular immune responses were studied in CsA-treated nonhuman primates having Chlamydia trachomatis proctitis (lymphogranuloma venereum, LGV). There was no apparent effect of CsA treatment on the gross or microscopic appearance of LGV proctitis, but CsA-treated animals, with or without LGV infection, had lymphoid hyperplasia of spleen and mesenteric lymph nodes. CsA treatment inhibited the primary antibody response to LGV, inhibited peripheral blood lymphocyte mitogen-i…

Head-to-head comparison of [18F]CHL2205 versus [18F]T008 as PET radioligands to study brain cholesterol homeostasis in rodent models and nonhuman primates.

PURPOSE: Cholesterol 24-hydroxylase (C24H) is central to brain cholesterol metabolism and is thought to be altered in many neurodegenerative … expressing mice. Arterial blood sampling enabled full kinetic modeling in healthy rats and nonhuman primates. An image-derived input function was validated in rats, and the specific binding was evaluated under C24H saturation using soticlestat. RESULTS: [¹⁸F]CHL-2205 and [¹⁸F]T008 showed similar metabolism profiles in either macaques or rats. In macaques, …

Generation of a Transgenic Plasmodium cynomolgi Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Testing P. vivax CSP-Based Malaria Vaccines in Non-Human Primates.

Background/Objectives: Malaria, caused by infection with Plasmodium parasites, exacts a heavy toll worldwide. There are two licensed vaccine … e which is genotypically very close and phenotypically similar to P. vivax; it can infect non-human primates commonly used in research and replicates many features of P. vivax, including relapsing hypnozoites. Methods: Recently, a strain of P. cynomolgi has been adapted to in vitro cultures allowing parasite transgenesis. Here, we created a transgenic P. c …

Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates.

Current influenza vaccines face challenges due to antigenic evolution of the circulating virus and waning immunity in humans. Here we investigated the durability of humoral immunity induced by an influenza vaccine based on AS03-adjuvanted chimeric hemagglutinin (cHA) in nonhuman primates (NHPs). Two groups of NHPs received two doses of a seasonal quadrivalent influenza vaccine, followed by sequential immunization with split virus cHA vaccines cH8/1N1, and cH5/1N1. One group received cHA immunizations with AS03 adjuvant. We monitored serum antibodies and long-lived plasma cells in bone marrow f…

A Preliminary Study on the Accuracy of MRI-Guided Thalamic Infusion of AAV2-GFP and Biodistribution Analysis Using Cryo-Fluorescence Tomography in Nonhuman Primates.

Background: Adeno-associated viral (AAV) vectors are the leading platform for gene therapy, but common delivery routes show limited spread to distal cortical structures, hence the utility of direct, intrathalamic infusions for broader transgene distribution. In this preliminary study, we recapitulate previous studies targeting the thalamus as a conduit to achieve cortical transgene spread and showcase novel data evaluating biodistribution of a green fluorescent protein (GFP) using cryo-fluorescence tomography (CFT). For the first time in nonhuman primates (NHPs) and coupled with magnetic reson…

Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system.

BACKGROUND: Achieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studie

Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates.

Tuberculosis remains a major health threat globally and a more effective vaccine than the current Bacillus Calmette Guerin (BCG) is required, either to replace or boost it. The Spore-FP1 mucosal vaccine candidate is based on the fusion protein of Ag85B-Acr-HBHA/heparin-binding domain, adsorbed on the surface of inactivated Bacillus subtilis spores. The candidate conferred significant protection against Mycobacterium. tuberculosis challenge in naïve guinea pigs and markedly improved protection in the lungs and spleens of animals primed with BCG. We then immunized rhesus macaques with BCG intrad

Corticotropin Releasing Factor (CRF) Coexpression in GABAergic, Glutamatergic, and GABA/Glutamatergic Subpopulations in the Central Extended Amygdala and Ventral Pallidum of Young Male Primates.

The central extended amygdala (CEA) and ventral pallidum (VP) are involved in diverse motivated behaviors based on rodent models. These structures are conserved, but expanded, in higher primates, including human. Corticotropin releasing factor (CRF), a canonical "stress molecule" associated with the CEA and VP circuitry across species, is dynamically regulated by stress and drugs of abuse and misuse. CRF's effects on circuits critically depend on its colocation with primary "fast" transmitters, making this crucial for understanding circuit effects. We surveyed the distribution and colocalizati…

Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine.

The ongoing pandemic of coronavirus (CoV) disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. … onstrate the protective efficacy of a VSV-EBOV-based COVID-19 vaccine against challenge in nonhuman primates (NHPs). When a single dose of the VSV-SARS2-EBOV vaccine was administered intramuscularly (i.m.), the NHPs were protected from COVID-19 within 10 days. In contrast, if the vaccine was administered intranasally, there was no benefit from the vaccine …

Neotropical Sylvatic Mosquitoes and Aedes aegypti Are Not Competent to Transmit 17DD Attenuated Yellow Fever Virus from Vaccinated Viremic New World Non-Human Primates.

Beside humans, thousands of non-human primates (NHPs) died during the recent outbreak caused by the yellow fever virus (YFV) in Brazil. Vaccination of NHPs against YFV with the YF 17DD attenuated virus has emerged as a public health strategy, as it would reduce sylvatic transmission while also preserving endangered susceptible species. The hypothesis of establishing an uncontrolled transmission of this attenuated virus in nature was raised. We assessed vector competence of four sylvatic mosquito species, Haemagogus leucocelaenus, Haemagogus janthinomys/capricornii, Sabethes albiprivus, and Sab…

Иммуногенность, создаваемая вакциной MRNA, кодирующей VZV gE антиген, сопоставима с прилегающей вакциной субъекта и лучше, чем живая вакцина в нечеловеческих приматах.

Синглс является болезненной, вспыльчивой сыпью, вызванной возобновлением скрытого вируса варицелла-зостера (VZV) и чаще всего происходит у пожилых и иммунокомпромиссированных лиц. В настоящее время на рынке имеются две утвержденные вакцины для профилактики шинглов: живая вирусная вакцина ZOSTAVAX (Merck & Co., Inc., Kenilworth, NJ, USA) и вакцина AS01B, прилегающая к протеинам, ShingrixTM (Glaxo Smith Kline, Rockville, MD, USA). По этим двум эталонным вакцинам имеются данные о клинической иммуногенности человека и эффективности вакцин, что открывает уникальную возможность для проведения сравни

Совпадение в аннотации оригинала
Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly a … e platforms and animal model translatability studies. The studies presented here utilized non-human primates (NHP) to evaluate humoral and cellular immune response by three vaccine modalities: the new platform of lipid nanoparticle (LNP) formulated mRNA encoding VZV gE antigen (VZV gE mRNA/LNP) as compared with well-established platforms of live attenuated …