scholarly journals Immunogenicity of a Candidate DTacP-sIPV Combined Vaccine and Its Protection Efficacy against Pertussis in a Rhesus Macaque Model

Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 47
Author(s):  
Xiaoyu Wang ◽  
Na Gao ◽  
Jiana Wen ◽  
Jingyan Li ◽  
Yan Ma ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Cellular Response ◽  
Clinical Symptoms ◽  
Rhesus Macaques ◽  
Polio Eradication ◽  
Control Group ◽  
Type I ◽  
Macaque Model ◽  
Protection Efficacy ◽  
Combined Vaccine

The research and development of a pertussis-combined vaccine using a novel inactivated poliovirus vaccine made from the Sabin strain (sIPV) is of great significance in the polio eradication project and to address the recent resurge in pertussis. In the present study, we compared the immunogenicity and efficacy of a candidate DTacP-sIPV with those of a commercial DTacP-wIPV/Hib, DTaP/Hib, pertussis vaccine, and aluminum hydroxide adjuvant control in the rhesus macaque model with a 0-, 1-, and 2-month immunization schedule. At day 28 after the third dose, rhesus macaques were challenged with aerosol pertussis and the antibody and cellular response together with pertussis clinical symptoms were determined. The production of anti-PT, anti-PRN, anti-FHA, anti-DT, anti-TT, and polio type I, II, III antibodies was induced by the candidate DTacP-sIPV, which was as potent as commercial vaccines. In comparison with the control group that showed typical pertussis symptoms of humans after the aerosol challenge, the DTacP-sIPV group did not exhibit obvious clinical pertussis symptoms and had higher neutralization titers of anti-PT, anti-PRN, and anti-FHA. In conclusion, the DTacP-sIPV vaccine was able to induce immunity in rhesus macaques to prevent pertussis infections after immunization. The developed vaccine was as efficient as other commercial vaccines.

scholarly journals Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidium chiangraiensis Chiggers

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1028
Author(s):  
Piyada Linsuwanon ◽  
Sirima Wongwairot ◽  
Nutthanun Auysawasdi ◽  
Taweesak Monkanna ◽  
Allen L. Richards ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Vaccine Development ◽  
Scrub Typhus ◽  
Rhesus Macaques ◽  
Disease Onset ◽  
Immunological Response ◽  
Pathogen Transmission ◽  
Type I ◽  
Orientia Tsutsugamushi ◽  
Macaque Model

Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, Orientia tsutsugamushi-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated O. tsutsugamushi in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit O. tsutsugamushi to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of O. tsutsugamushi within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that O. tsutsugamushi infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.

scholarly journals Anti-α4β7 monoclonal antibody–conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques

2020 ◽  
Vol 6 (34) ◽  
pp. eabb9853
Author(s):  
Sidi Yang ◽  
Geraldine Arrode-Bruses ◽  
Ines Frank ◽  
Brooke Grasperge ◽  
James Blanchard ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Single Dose ◽  
Side Effects ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Vaginal Infection ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Vaginal Tract

Intravenous administration of anti-α4β7 monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-α4β7 antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α4β7 monoclonal antibody–conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α4β7 gel). When intravaginally administered as a single dose in a rhesus macaque model, the formulation preferentially bound to CD4+ or CD3+ T cells expressing high levels of α4β7, and occupied ~40% of α4β7 expressed by these subsets and ~25% of all cells expressing α4β7. Blocking of the α4β7 was restricted to the vaginal tract without any changes detected systemically.

scholarly journals In Vivo Antiviral Effects of U18666A Against Type I Feline Infectious Peritonitis Virus

Pathogens ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Tomoyoshi Doki ◽  
Tomoyo Tarusawa ◽  
Tsutomu Hohdatsu ◽  
Tomomi Takano
Keyword(s):  
Clinical Symptoms ◽  
Treated Group ◽  
Control Group ◽  
Type I ◽  
Feline Infectious Peritonitis Virus ◽  
Feline Infectious Peritonitis ◽  
Amphiphilic Drug ◽  
Antiviral Effects

Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg/kg on day 0, and 1.25 mg/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.

scholarly journals The intensity of the immune response to LPS and E. coli regulates the induction of preterm labor in Rhesus Macaques

2021 ◽  
Author(s):  
Monica Cappelletti ◽  
Pietro Presicce ◽  
Feyiang Ma ◽  
Paranthaman Senthamaraikannan ◽  
Lisa Miller ◽  
...  
Keyword(s):  
Immune Response ◽  
Rhesus Macaque ◽  
Preterm Labor ◽  
Iron Homeostasis ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Neutrophil Infiltration ◽  
Interferon Response ◽  
Type I ◽  
E Coli

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed Rhesus macaque models of IUI driven by lipopolysaccharyde (LPS) or live  E. coli . PTL did not occur in LPS challenged Rhesus macaque while  E. coli  infected animals frequently delivered preterm. Although LPS and live  E. coli  both caused immune cell infiltration,  E. coli  infected animals showed higher levels of inflammatory mediators, particularly IL6 and prostaglandins, in the chorioamnion decidua and amniotic fluid. Neutrophil infiltration in the chorion was a common feature to both LPS and  E. coli . However, neutrophilic infiltration and  IL6 and PTGS2 expression in the amnion was specifically induced by live  E. coli . RNASeq analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon response, chemotaxis, sumoylation and iron homeostasis were upregulated in the  E. coli group compared to the LPS group. Our data suggest that intensity of the host immune response to IUI may determine susceptibility to PTL.

scholarly journals Exocrine pancreatic dysfunction in children with obesity: characteristics of clinical picture and diagnostics

2020 ◽  
pp. 36-41
Author(s):  
I. S. Lembryk ◽  
O. V. Tymoshchuk
Keyword(s):  
Abdominal Pain ◽  
Clinical Symptoms ◽  
High Density Lipoproteins ◽  
Exocrine Function ◽  
Control Group ◽  
Type I ◽  
Healthy Children ◽  
Obese Children ◽  
Pancreatic Lesion ◽  
Functional Changes

Introduction. During the last twenty-five years the occurrence of obesity in children and teenagers has increased significantly. Materials and methods. 110 adolescents of 12–17 years old, with alimentary-constitutional obesity and involvement of pancreas and without its injury, as compared to the 30 healthy children of control group, were examined. The research provided determination of the sizes and elasticity of pancreas. The detection of the total cholesterol, high density lipoproteins and leptin level was carried out. Intensity of clinical symptoms (spastic pain in epigastrium and left subcostal arc; abdominal pain without localization, vomit without relief, general weakness) have been made accordingly to sum of points (from 0 to 3 points). If sum of points makes from 0 to 2 – intensive character of abdominal pain is low, from 3 to 5 points – it is high, from 5 to 10 points – it is very high. Normal level of amylase in a blood serum (Karavey’s method) is 12–32 g/(hour l), аnd diastase in urine – 20–160 g/(hour l). We made a screening test for elastase-I level by ELISA test. Normal activity of this enzyme in feces is 200 мkg/g. We have used sonographic method for detection of pancreatic diseases in obese children due to echo-structure of parotid gland. The analysis and statistical data processing were made by computer program "Statistica 7.0" and MS Excel XP. Research data. Physical inspection of our patients confirms prevalence of І degree over II degree obesity (52.7 % and 47.3 %, respectively; Р < 0.05). We have confirmed valid risk factor of pancreatic lesion in obese children – presence of diabetes mellitus type I in close relatives (80 % and 65 %, χ2 = 2,05; Р < 0.05). The changes of exocrine function of the pancreas in children with the stage II obesity were established. Echographic signs of the pancreas lesion in teenagers with obesity indicate the presence of functional changes: edema of head or entire edema, partial increase of parenchymal echogenicity, insufficient enlargement of the duct of Wirsung.

scholarly journals Therapeutic effects of combined meloxicam and glucosamine sulfate treatment on patients with osteoarthritis, and its effect on serum CTX-Ⅰ, CTX-Ⅱ, COMP and MMP-3

2021 ◽  
Vol 18 (7) ◽  
pp. 1553-1557
Author(s):  
Lu Zhijun ◽  
Chen Rongchun ◽  
Lin Feixiang ◽  
Wu Yaohong ◽  
Liu Ning ◽  
...  
Keyword(s):  
Treatment Group ◽  
Matrix Protein ◽  
Type I Collagen ◽  
Clinical Symptoms ◽  
Type Ii Collagen ◽  
Symptomatic Treatment ◽  
Glucosamine Sulfate ◽  
Control Group ◽  
Therapeutic Effects ◽  
Type I

Purpose: To study the therapeutic influence of meloxicam-glucosamine sulfate combination in patients with osteoarthritis and their effect on serum CTX-I, CTX-II, COMP and MMP-3. Methods: A total of 88 patients with osteoarthritis were assigned to control (n = 44) and treatment groups (n = 44), using the random number table method. Control group was given 7.5 mg of meloxicam, while treatment group received 0.5 g of glucosamine sulfate capsule in addition to meloxicam. Both groups were treated continuously for 8 weeks. Serum levels of C-terminal telopeptide of type I collagen (CTX-I), C-terminal telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-3 (MMP-3) were compared for the two groups after treatment. Results: Lysholm score significantly increased in the two groups after treatment. Serum CTX-I, CTX-II, COMP and MMP-3 in the two groups were significantly lower than before treatment, but the reductions were more pronounced in the treatment group (p < 0.05). During treatment, mild vomiting and pruritus of the skin appeared in both groups, but these were relieved after symptomatic treatment without any serious adverse reactions. Conclusion: Treatment with a combination of meloxicam and glucosamine sulfate produces significant beneficial effects in patients with osteoarthritis by reduction of clinical symptoms, pain relief and reduction of serum CTX-I, CTX-II, MMP-3 and COMP.

scholarly journals A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

2021 ◽  
Author(s):  
Paul E. Harris ◽  
Trevor Brasel ◽  
Christopher Massey ◽  
C. V. Herst ◽  
Scott Burkholz ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Clinical Symptoms ◽  
Rhesus Macaques ◽  
Peptide Vaccine ◽  
Hla Class I ◽  
Class I ◽  
Vaccination Programs ◽  
Macaque Model ◽  
Unvaccinated Control ◽  
Downstream Analysis

AbstractBackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, 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.MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.Graphical Abstract

scholarly journals Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation

2015 ◽  
Vol 112 (49) ◽  
pp. 15142-15147 ◽  
Author(s):  
Steven W. Cole ◽  
John P. Capitanio ◽  
Katie Chun ◽  
Jesusa M. G. Arevalo ◽  
Jeffrey Ma ◽  
...  
Keyword(s):  
Social Isolation ◽  
Rhesus Macaques ◽  
Transcriptional Response ◽  
Population Expansion ◽  
Myeloid Cell ◽  
Type I ◽  
Cellular Mechanisms ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Perceived Social Isolation

To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14++/CD16−classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.

scholarly journals A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 520
Author(s):  
Paul E. Harris ◽  
Trevor Brasel ◽  
Christopher Massey ◽  
C. V. Herst ◽  
Scott Burkholz ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Clinical Symptoms ◽  
Rhesus Macaques ◽  
Peptide Vaccine ◽  
Hla Class I ◽  
Class I ◽  
Vaccination Programs ◽  
Macaque Model ◽  
Unvaccinated Control ◽  
Downstream Analysis

Background: 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. Methods: Using a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 × 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms and viral load, chest radiographs, and sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis. Results: Vaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques. Conclusions: We demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in nonhuman primates.

scholarly journals Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development

2021 ◽  
Vol 9 (3) ◽  
pp. 489
Author(s):  
Kendra J. Alfson ◽  
Yenny Goez-Gazi ◽  
Michal Gazi ◽  
Hilary Staples ◽  
Marc Mattix ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Ebola Virus ◽  
Virus Disease ◽  
Rna Virus ◽  
Rhesus Macaques ◽  
Systemic Disease ◽  
Clinical Pathology ◽  
Macaque Model ◽  
Progression Of Disease ◽  
Ebov Infection

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 intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger-to-treat” for use in therapeutic studies.

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