Non-human Primate Research in Immune Modulation and Drug Discovery

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Innate and Adaptive Immunity in Vaccination".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 29639

Special Issue Editors


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Guest Editor
Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, 75015 Paris, France Institut Pasteur, Unité HIV Inflammation et Persistance, 75015 Paris, France
Interests: HIV/SIV; pathogenesis; non-human primate models; natural and post-treatment control; reservoir; T-cell responses; immune modulation; biomarkers; immunometabolism

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Guest Editor
Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, 75015 Paris, France
Interests: HIV/SIV; natural host; AGM; macaque; pathogenesis; innate immunity

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Guest Editor
Inserm, Immunology of viral infections and autoimmune diseases, Paris, France
Interests: vaccine; adjuvant; innate immunity; trained immunity; non-human primates; mass cytometry

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Guest Editor
Institution of Johns Hopkins Medicine School, Baltimore, MD, USA
Interests: HIV/SIV; animal model; inflammation; cellular activation; reservoir; viral latency; myeloid and CD4+ T-cells; latency assays (QVOA and IPDA)

Special Issue Information

Dear Colleagues,

Studies using non-human primates (NHP) are at the origin of major scientific discoveries that have led to improvements in human health over the past years. Due to their close similarity to human physiology and genetics, NHP represent the most valuable animal model for numerous diseases and play a central role in translational research to develop vaccines, drugs, and other interventions.
This Special Issue of Vaccines is open to original research manuscripts, short communications, perspectives, or reviews focusing on recent advances in immune modulation and drug discovery using NHP models. The submission of articles covering the following research areas is encouraged:

  • Development and characterization of NHP models for immune modulation and drug discovery;
  • Experimental characterization of immune interventions in NHP models;
  • Proof of concept drug development and immune interventions in NHP models;
  • Prophylactic and therapeutic translational research.

Dr. Caroline Pereira Bittencourt Passaes
Dr. Beatrice Jacquelin
Dr. Anne-Sophie Beignon
Dr. Celina Monteiro Abreu
Guest Editors

Manuscript Submission Information

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Keywords

  • Non-human primate
  • animal models
  • translational research
  • immune modulation
  • immune intervention
  • immunotherapy
  • drug discovery
  • treatment
  • prophylaxis
  • cure

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Published Papers (6 papers)

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Research

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17 pages, 4516 KiB  
Article
Ex Vivo Evaluation of Mucosal Responses to Vaccination with ALVAC and AIDSVAX of Non-Human Primates
by Carolina Herrera, Ronald Veazey, Melissa M. Lemke, Kelly Arnold, Jerome H. Kim and Robin J. Shattock
Vaccines 2022, 10(2), 187; https://doi.org/10.3390/vaccines10020187 - 25 Jan 2022
Cited by 2 | Viewed by 2698
Abstract
Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured [...] Read more.
Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1CM244-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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17 pages, 2217 KiB  
Article
p38γ Activation and BGP (Biliary Glycoprotein) Induction in Primates at Risk for Inflammatory Bowel Disease and Colorectal Cancer—A Comparative Study with Humans
by Harvinder Talwar, Benita McVicker and Martin Tobi
Vaccines 2020, 8(4), 720; https://doi.org/10.3390/vaccines8040720 - 2 Dec 2020
Cited by 6 | Viewed by 2348
Abstract
Colorectal cancer (CRC) is a common cause of cancer-related deaths largely due to CRC liver metastasis (CRLM). Identification of targetable mechanisms continues and includes investigations into the role of inflammatory pathways. Of interest, MAPK is aberrantly expressed in CRC patients, yet the activation [...] Read more.
Colorectal cancer (CRC) is a common cause of cancer-related deaths largely due to CRC liver metastasis (CRLM). Identification of targetable mechanisms continues and includes investigations into the role of inflammatory pathways. Of interest, MAPK is aberrantly expressed in CRC patients, yet the activation status is not defined. The present study assessed p38γ activation in CRC patients, cancer cells, and tissues of cotton top tamarin (CTT) and common marmoset (CM). The primate world is an overlooked resource as colitis-CRC-prone CTT are usually inure to liver metastasis while CM develop colitis but not CRC. The results demonstrate that p38γ protein and phosphorylation levels are significantly increased in CRC patients compared to normal subjects and CTT. Furthermore, p38γ phosphorylation is significantly elevated in human CRC cells and hepatoblastoma cells but not in CM colon. Additionally, carcinoembryonic antigen (CEA) and biliary glycoprotein (BGP) are induced in the CRC patients that showed p38γ phosphorylation. Inhibition of p38 MAPK in CRC cells showed a significant decline in cell growth with no effect on apoptosis or BGP level. Overall, p38γ is activated in CRC tumorigenesis and likely involves CEA antigens during CRLM in humans but not in the CTT or CM, that rarely develop CRLM. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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Review

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24 pages, 1625 KiB  
Review
Interests of the Non-Human Primate Models for HIV Cure Research
by Gauthier Terrade, Nicolas Huot, Caroline Petitdemange, Marie Lazzerini, Aurelio Orta Resendiz, Beatrice Jacquelin and Michaela Müller-Trutwin
Vaccines 2021, 9(9), 958; https://doi.org/10.3390/vaccines9090958 - 27 Aug 2021
Cited by 10 | Viewed by 4500
Abstract
Non-human primate (NHP) models are important for vaccine development and also contribute to HIV cure research. Although none of the animal models are perfect, NHPs enable the exploration of important questions about tissue viral reservoirs and the development of intervention strategies. In this [...] Read more.
Non-human primate (NHP) models are important for vaccine development and also contribute to HIV cure research. Although none of the animal models are perfect, NHPs enable the exploration of important questions about tissue viral reservoirs and the development of intervention strategies. In this review, we describe recent advances in the use of these models for HIV cure research and highlight the progress that has been made as well as limitations using these models. The main NHP models used are (i) the macaque, in which simian immunodeficiency virus (SIVmac) infection displays similar replication profiles as to HIV in humans, and (ii) the macaque infected by a recombinant virus (SHIV) consisting of SIVmac expressing the HIV envelope gene serving for studies analyzing the impact of anti-HIV Env broadly neutralizing antibodies. Lessons for HIV cure that can be learned from studying the natural host of SIV are also presented here. An overview of the most promising and less well explored HIV cure strategies tested in NHP models will be given. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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29 pages, 915 KiB  
Review
COVID-19 Research: Lessons from Non-Human Primate Models
by Laure Albrecht, Elodie Bishop, Basile Jay, Blaise Lafoux, Marie Minoves and Caroline Passaes
Vaccines 2021, 9(8), 886; https://doi.org/10.3390/vaccines9080886 - 10 Aug 2021
Cited by 22 | Viewed by 6803
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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15 pages, 10332 KiB  
Review
Preclinical Marmoset Model for Targeting Chronic Inflammation as a Strategy to Prevent Alzheimer’s Disease
by Ingrid H. C. H. M. Philippens and Jan A. M. Langermans
Vaccines 2021, 9(4), 388; https://doi.org/10.3390/vaccines9040388 - 15 Apr 2021
Cited by 7 | Viewed by 3489
Abstract
Due to the aging population, modern society is facing an increasing prevalence of neurological diseases such as Alzheimer’s disease (AD). AD is an age-related chronic neurodegenerative disorder for which no satisfying therapy exists. Understanding the mechanisms underlying the onset of AD is necessary [...] Read more.
Due to the aging population, modern society is facing an increasing prevalence of neurological diseases such as Alzheimer’s disease (AD). AD is an age-related chronic neurodegenerative disorder for which no satisfying therapy exists. Understanding the mechanisms underlying the onset of AD is necessary to find targets for protective treatment. There is growing awareness of the essential role of the immune system in the early AD pathology. Amyloidopathy, the main feature of early-stage AD, has a deregulating effect on the immune function. This is reciprocal as the immune system also affects amyloidopathy. It seems that the inflammatory reaction shows a heterogeneous pattern depending on the stage of the disease and the variation between individuals, making not only the target but also the timing of treatment important. The lack of relevant translational animal models that faithfully reproduce clinical and pathogenic features of AD is a major cause of the delay in developing new disease-modifying therapies and their optimal timing of administration. This review describes the communication between amyloidopathy and inflammation and the possibility of using nonhuman primates as a relevant animal model for preclinical AD research. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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16 pages, 9803 KiB  
Review
Opportunities for Refinement of Non-Human Primate Vaccine Studies
by Mark J. Prescott, Carolyn Clark, William E. Dowling and Amy C. Shurtleff
Vaccines 2021, 9(3), 284; https://doi.org/10.3390/vaccines9030284 - 19 Mar 2021
Cited by 7 | Viewed by 8087
Abstract
Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of [...] Read more.
Non-human primates (NHPs) are used extensively in the development of vaccines and therapeutics for human disease. High standards in the design, conduct, and reporting of NHP vaccine studies are crucial for maximizing their scientific value and translation, and for making efficient use of precious resources. A key aspect is consideration of the 3Rs principles of replacement, reduction, and refinement. Funders of NHP research are placing increasing emphasis on the 3Rs, helping to ensure such studies are legitimate, ethical, and high-quality. The UK’s National Centre for the 3Rs (NC3Rs) and the Coalition for Epidemic Preparedness Innovations (CEPI) have collaborated on a range of initiatives to support vaccine developers to implement the 3Rs, including hosting an international workshop in 2019. The workshop identified opportunities to refine NHP vaccine studies to minimize harm and improve welfare, which can yield better quality, more reproducible data. Careful animal selection, social housing, extensive environmental enrichment, training for cooperation with husbandry and procedures, provision of supportive care, and implementation of early humane endpoints are features of contemporary good practice that should and can be adopted more widely. The requirement for high-level biocontainment for some pathogens imposes challenges to implementing refinement but these are not insurmountable. Full article
(This article belongs to the Special Issue Non-human Primate Research in Immune Modulation and Drug Discovery)
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