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Immuno-toxicological evaluation of her1 cancer vaccine in non-human primates: a 6-month subcutaneous study

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY 2021年第3期43卷 283-290页

作者： Mancebo Rodriguez, Axel Bergado Baez, Gretchen Acosta Lago, Eric Leon Goni, Avelina Blanco Gamez, Diuris Fuentes Morales, Dasha Hernandez Fernandez, Diana Rosa Sanchez Ramirez, Belinda Perez Barreda, Aylen Casaco Parada, Angel Natl Ctr Lab Animals Breeding CENPALAB Ctr Expt Toxicol Havana Cuba Ctr Mol Immunol CIM Tumor Immunol Direct Havana Cuba Ctr Med Surg Res CIMEQ Havana Cuba

Purpose: A vaccine composition based on the extracellular domain of the human epidermal growth factor receptor 1 (HER1-ECD) and the combination of VSSP (very small size proteoliposomes) and Montanide ISA 51 adjuvants when used by intramuscular route, demonstrated promising results in preclinical studies. However, in order to avoid potential adverse events due to the use of Montanide, it is proposed to modify the vaccine formulation by using VSSP (very small size proteoliposomes) adjuvant alone, and to evaluate the quality of subcutaneously induced immune response. This study aimed to assess the immunotoxicological effects of HER1 vaccine in cercopithecus aethiops. Materials and methods: Fifteen monkeys were randomized into four groups: Negative Control (Tris/NaCl, s.c.), Positive Control (200 mu g HER1-ECD/VSSP/Montanide ISA-51 VG, i.m), Low Dose (200 mu g HER1-ECD/VSSP/Tris NaCl, s.c.) and High Dose (800 mu g HER1-ECD/VSSP/Tris NaCl, s.c). All monkeys received 7 doses and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study, and electrocardiographical and ophthalmological studies were performed. Humoral and cellular immune response and clinical pathology parameters were analyzed. Results: Animal's survival in the study was 100% (n = 15). Administration site reactions were observed in the Positive Control animals (n = 4). HER1 vaccine administered subcutaneously (High Dose Group) achieved good IgG antibody titers although lower than the Positive Control group, but with higher ability to inhibit HER1 phosphorylation. Conclusions: This suggests that the alternative of eliminating the use of Montanide in the HER1 vaccine preparation and the using subcutaneous route is feasible.

关键词： HER1 cancer vaccine repeated dose immunotoxicology cercopithecus aethiops

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Investigating The Host Range Of Neoromicia Capensis Coronavirus In Vitro

Investigating The Host Range Of Neoromicia Capensis Coronavi...

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作者： Andrea Kotze Stellenbosch University

学位级别：硕士

ENGLISH ABSTRACT: Coronaviruses are known to cause disease in humans and animals. Two important human coronaviruses that have caused epidemics are severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). These coronaviruses originated in animals and were introduced into the human population through zoonotic transmission. Neoromicia capensis coronavirus (NeoCoV), a bat coronavirus that was discovered in the South African bat species Neoromicia capensis, is 85.5% genetically identical to MERS-CoV. It is believed that NeoCoV is an ancestor of MERS-CoV; however, the potential for NeoCoV to emerge as a potential zoonotic agent has not yet been investigated. This study investigated the host range of NeoCoV in order to assess its potential to cross the species barrier from bats to other mammals. This study attempted to isolate NeoCoV in cell culture to investigate its behaviour in vitro. The host range of NeoCoV was further explored by developing viral pseudoparticles that expressed the spike proteins of NeoCoV, MERS-CoV or SARS-CoV. These pseudoparticles were used to infect various cell lines of mammalian origin to determine which animal species NeoCoV may be able to infect and if its host range has any similarities to that of MERS- and/or SARS-CoV. Attempts were made to isolate NeoCoV in cell culture by inoculating host-derived cells with NeoCoV-positive bat faecal homogenate. Attempts were proven unsuccessful by a highly sensitive quantitative reverse transcription polymerase chain reaction assay. Infecting cell lines with pseudoparticles bearing either the NeoCoV, MERS- or SARS-CoV spike protein revealed that NeoCoV could possibly utilise N. capensis kidney cells for replication, and not the lungs or trachea. Infection of Pipistrellus pipistrellus kidney cells with the three different pseudotypes yielded low levels of infection, suggesting that this cell line is less susceptible to infection by the three viru

关键词： Coronavirus infections cercopithecus aethiops Pipistrellus Kidney toxicity

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History and Status of Introduced Non-human Primate Populations in Florida

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SOUTHEASTERN NATURALIST 2017年第1期16卷 19-36页

作者： Anderson, C. Jane Hostetler, Mark E. Johnson, Steve A. Univ Florida Sch Nat Resources & Environm 110 Newins Ziegler HallPOB 110430 Gainesville FL 32611 USA Univ Florida Dept Wildlife Ecol & Conservat 110 Newins Ziegler HallPOB 110430 Gainesville FL 32611 USA

We validated and synthesized reports of historic and current populations of the 3 introduced non-human primate species in Florida-Saimiri sp. (squirrel monkey), Chlorocebus sabaeus (Vervet Monkey), and Macaca mulatta (Rhesus Macaque)-using systematic review of literature, content analysis of popular media, expert interviews, and site visits. Invasion success varied among the 3 species: only 1 of 5 squirrel monkey populations was still extant, a single Vervet Monkey population showed little change between the mid-1990s and 2015, and 2 of 3 introduced Rhesus Macaque populations grew, but only 1 was extant. Disparities in invasion success appeared to be primarily influenced by natural history and anthropogenic intervention. Understanding introduced species success is critical to determine current and potential impacts and effectively allocate limited management resources.

关键词： PRIMATE populations cercopithecus aethiops HISTORY MAMMAL populations

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Inactivation of Zika virus in platelet components using amotosalen and ultraviolet A illumination

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TRANSFUSION 2017年第8期57卷 2016-2025页

作者： Santa Maria, Felicia Laughhunn, Andrew Lanteri, Marion C. Aubry, Maite Musso, Didier Stassinopoulos, Adonis Cerus Corp 2550 Stanwell Dr Concord CA 94520 USA Inst Louis Malarde Pole Rech & Veille Malad Infect Emergentes Tahiti French Polynesi France

BACKGROUND: Concerned over the risk of Zika virus (ZIKV) transfusion transmission, public health agencies recommended the implementation of mitigation strategies for its prevention. Those strategies included the use of pathogen inactivation for the treatment of plasma and platelets. The efficacy of amotosalen/ultraviolet A to inactivate ZIKV in plasma had been previously demonstrated, and the efficacy of inactivation in platelets with the same technology was assumed. These studies quantify ZIKV inactivation in platelet components using amotosalen/ultraviolet A. STUDY DESIGN AND METHODS: Platelet components were spiked with ZIKV, and ZIKV infectious titers and RNA loads were measured by cell culture-based assays and real-time polymerase chain reaction in spiked platelet components before and after photochemical treatment using amotosalen/ultraviolet A. RESULTS: The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 log(10) plaque forming units per milliliter, or 4.4 log(10) 50% tissue culture infective dose per milliliter and 7.5 log(10) genome equivalents per milliliter, respectively. No infectivity was detected immediately after amotosalen/ultraviolet A treatment. No replicative virus remained after treatment, as demonstrated by multiple passages on Vero cell cultures;and ZIKV RNA was not detected from the first passage after inactivation. Additional experiments in this study demonstrated efficient inactivation to the limit of detection in platelets manufactured in 65% platelet additive solution, 35% plasma, or 100% plasma. CONCLUSION: As previously demonstrated for plasma, robust levels of ZIKV inactivation were achieved in platelet components. With inactivation of higher levels of ZIKV than those reported in asymptomatic, RNA-reactive blood donors, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion.

关键词： Animals Blood Platelets/virology cercopithecus aethiops Furocoumarins/pharmacology Humans Platelet Transfusion/adverse effects RNA, Viral Ultraviolet Rays Ultraviolet Rays Vero Cells Viral Load Viral Load Virus Inactivation/drug effects Virus Inactivation/drug effects Virus Inactivation/radiation effects Virus Inactivation/radiation effects Zika Virus/drug effects Zika Virus/radiation effects Zika Virus Infection/prevention & control Zika Virus Infection/transmission

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Cardiac safety pharmacology in the St. Kitts African green monkey

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JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS 2018年 93卷 122-122页

作者： Banerjee, Aryamitra Liddie, Shervin Moddrelle, David Lindeblad, Matthew Chen, Yongmei Lyubimov, Alexander Lawrence, Matthew RxGen New Haven CT USA Toxicol Res Lab Chicago IL USA

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Genomic comparison of drug metabolizing enzymes in African green monkeys versus other species

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JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS 2018年 93卷 140-140页

作者： Banerjee, Aryamitra Attwood, Jordan Lawrence, Matthew RxGen New Haven CT USA

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Transmission of Staphylococcus aureus from Humans to Green Monkeys in The Gambia as Revealed by Whole-Genome Sequencing

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APPLIED AND ENVIRONMENTAL MICROBIOLOGY 2016年第19期82卷 5910-5917页

作者： Senghore, Madikay Bayliss, Sion C. Kwambana-Adams, Brenda A. Foster-Nyarko, Ebenezer Manneh, Jainaba Dione, Michel Badji, Henry Ebruke, Chinelo Doughty, Emma L. Thorpe, Harry A. Jasinska, Anna J. Schmitt, Christopher A. Cramer, Jennifer D. Turner, Trudy R. Weinstock, George Freimer, Nelson B. Pallen, Mark J. Feil, Edward J. Antonio, Martin MRC Unit Fajara Gambia Univ Warwick Coventry W Midlands England Univ Bath Bath Avon England Univ Calif Los Angeles Los Angeles CA USA Amer Mil Univ Charles Town WV USA Amer Publ Univ Charles Town WV USA Univ Wisconsin Milwaukee WI 53201 USA Univ Free State Bloemfontein South Africa Washington Univ St Louis MO USA London Sch Hyg & Trop Med London England Int Livestock Res Inst Kampala Uganda Boston Univ Boston MA 02215 USA Jackson Lab Genom Med Farmington CT USA

Staphylococcus aureus is an important pathogen of humans and animals. We genome sequenced 90 S. aureus isolates from The Gambia: 46 isolates from invasive disease in humans, 13 human carriage isolates, and 31 monkey carriage isolates. We inferred multiple anthroponotic transmissions of S. aureus from humans to green monkeys (Chlorocebus sabaeus) in The Gambia over different time scales. We report a novel monkey-associated clade of S. aureus that emerged from a human-to-monkey switch estimated to have occurred 2,700 years ago. Adaptation of this lineage to the monkey host is accompanied by the loss of phage-carrying genes that are known to play an important role in human colonization. We also report recent anthroponotic transmission of the well-characterized human lineages sequence type 6 (ST6) and ST15 to monkeys, probably because of steadily increasing encroachment of humans into the monkeys' habitat. Although we have found no evidence of transmission of S. aureus from monkeys to humans, as the two species come into ever-closer contact, there might be an increased risk of additional interspecies exchanges of potential pathogens.

关键词： STAPHYLOCOCCUS aureus infections cercopithecus aethiops DNA sequencing RIBOSOMAL RNA PUBLIC health TRANSMISSION GAMBIA

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Astrocytes Assemble Thalamocortical Synapses by Bridging NRX1α and NL1 via Hevin

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CELL 2016年第1-2期164卷 183-196页

作者： Singh, Sandeep K. Stogsdill, Jeff A. Pulimood, Nisha S. Dingsdale, Hayley Kim, Yong Ho Pilaz, Louis-Jan Kim, Il Hwan Manhaes, Alex C. Rodrigues, Wandilson S., Jr. Pamukcu, Arin Enustun, Eray Ertuz, Zeynep Scheiffele, Peter Soderling, Scott H. Silver, Debra L. Ji, Ru-Rong Medina, Alexandre E. Eroglu, Cagla Duke Univ Med Ctr Dept Cell Biol Durham NC 27710 USA Univ Maryland Dept Pediat Sch Med Baltimore MD 21201 USA Duke Univ Med Ctr Dept Anesthesiol Durham NC 27710 USA Duke Univ Med Ctr Dept Mol Genet & Microbiol Durham NC 27710 USA Univ Basel Biozentrum CH-4056 Basel Switzerland Duke Univ Med Ctr Dept Neurobiol Durham NC 27710 USA DIBS Durham NC 27710 USA

Proper establishment of synapses is critical for constructing functional circuits. Interactions between presynaptic neurexins and postsynaptic neuroligins coordinate the formation of synaptic adhesions. An isoform code determines the direct interactions of neurexins and neuroligins across the synapse. However, whether extracellular linker proteins can expand such a code is unknown. Using a combination of in vitro and in vivo approaches, we found that hevin, an astrocyte-secreted synaptogenic protein, assembles glutamatergic synapses by bridging neurexin-1alpha and neuroligin-1B, two isoforms that do not interact with each other. Bridging of neurexin-1alpha and neuroligin-1B via hevin is critical for the formation and plasticity of thalamocortical connections in the developing visual cortex. These results show that astrocytes promote the formation of synapses by modulating neurexin/neuroligin adhesions through hevin secretion. Our findings also provide an important mechanistic insight into howmutations in these genes may lead to circuit dysfunction in diseases such as autism.

关键词： Animals Astrocytes/metabolism Calcium-Binding Proteins/metabolism Cell Adhesion Molecules, Neuronal/metabolism cercopithecus aethiops COS Cells Dominance, Ocular Extracellular Matrix Proteins/metabolism Humans Mice Mice, Knockout Mice, Knockout Nervous System Diseases/metabolism Neural Cell Adhesion Molecules/metabolism Neurons/metabolism Protein Isoforms/metabolism Signal Transduction Synapses/metabolism Thalamus/metabolism

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Model establishment for cardiovascular evaluation using the novel Stellar TSE's Type PPBTA-XL Telemetry Transmitter in the Vervet (St. Kitts green monkey)

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JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 2017年 112卷 153-153页

作者： Liddie, Shervin Banerjee, Aryamitra Moddrelle, David Morton, Xavier Lawrence, Matthew RxGen Inc New Haven CT USA

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Evolutionary insights from wild vervet genomes

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NATURE GENETICS 2017年第12期49卷 1671-1672页

作者： Leffler, Ellen M. Univ Oxford Wellcome Trust Ctr Human Genet Oxford England Wellcome Trust Sanger Inst Hinxton England

A new study reports genome-wide variation in 163 vervet monkeys from across their taxonomic and geographic ranges. The analysis suggests a complex history of admixture and identifies signals of repeated evolutionary s... 详细信息

关键词： Genome Genomics cercopithecus aethiops Chlorocebus Simian Immunodeficiency Virus Vervet Monkey Additives Evolutionary

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