Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research

Background Non-human primates (NHPs) play an important role in biomedical research, where they are often being re-used in multiple research studies over the course of their life-time. Researchers employ various study-specific screening criteria to reduce potential variables associated with subsequen...

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Main Authors: François A. Bates, Elizabeth H. Duncan, Monika Simmons, Tanisha Robinson, Sridhar Samineni, Natasa Strbo, Eileen Villasante, Elke Bergmann-Leitner, Wathsala Wijayalath
Format: Article
Language:English
Published: PeerJ Inc. 2021-03-01
Series:PeerJ
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Online Access:https://peerj.com/articles/10955.pdf
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author François A. Bates
Elizabeth H. Duncan
Monika Simmons
Tanisha Robinson
Sridhar Samineni
Natasa Strbo
Eileen Villasante
Elke Bergmann-Leitner
Wathsala Wijayalath
author_facet François A. Bates
Elizabeth H. Duncan
Monika Simmons
Tanisha Robinson
Sridhar Samineni
Natasa Strbo
Eileen Villasante
Elke Bergmann-Leitner
Wathsala Wijayalath
author_sort François A. Bates
collection DOAJ
description Background Non-human primates (NHPs) play an important role in biomedical research, where they are often being re-used in multiple research studies over the course of their life-time. Researchers employ various study-specific screening criteria to reduce potential variables associated with subsequent re-use of NHPs. However, criteria set for NHP re-assignments largely neglect the impact of previous exposures on overall biology. Since the immune system is a key determinant of overall biological outcome, an altered biological state could be predicted by monitoring global changes in the immune profile. We postulate that every different exposure or a condition can generate a unique global immune profile in NHPs. Methods Changes in the global immune profile were evaluated in three different groups of rhesus macaques previously enrolled in dengue or malaria vaccine studies over six months after their last exposure. Naïve animals served as the baseline. Fresh blood samples were stained with various immune cell surface markers and analyzed by multi-color flow-cytometry to study immune cell dynamics in the peripheral blood. Serum cytokine profile in the pre-exposed animals were analyzed by mesoscale assay using a customized U-PLEX NHP biomarker panel of 12 cytokines/chemokines. Results Pre-exposed macaques showed altered dynamics in circulating cytokines and certain innate and adaptive immune cell subsets such as monocytes, HLA-DR+NKT cells, B cells and T cells. Some of these changes were transient, while some lasted for more than six months. Each group seemed to develop a global immune profile unique to their particular exposure. Conclusion Our data strongly suggest that re-used NHPs should be evaluated for long-term, overall immunological changes and randomly assigned to new studies to avoid study bias.
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spelling doaj.art-2ac1142a83a449ccb5005bc7be1e21072023-12-03T10:37:39ZengPeerJ Inc.PeerJ2167-83592021-03-019e1095510.7717/peerj.10955Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in researchFrançois A. Bates0Elizabeth H. Duncan1Monika Simmons2Tanisha Robinson3Sridhar Samineni4Natasa Strbo5Eileen Villasante6Elke Bergmann-Leitner7Wathsala Wijayalath8Veterinary Services Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of AmericaImmunology Core/Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States of AmericaViral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States of AmericaImmunology Core/Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States of AmericaVeterinary Services Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of AmericaDepartment of Microbiology and Immunology, Miller School of Medicine University of Miami, Miami, FL, United States of AmericaMalaria Department, Naval Medical Research Center, Silver Spring, MD, United States of AmericaImmunology Core/Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States of AmericaMalaria Department, Naval Medical Research Center, Silver Spring, MD, United States of AmericaBackground Non-human primates (NHPs) play an important role in biomedical research, where they are often being re-used in multiple research studies over the course of their life-time. Researchers employ various study-specific screening criteria to reduce potential variables associated with subsequent re-use of NHPs. However, criteria set for NHP re-assignments largely neglect the impact of previous exposures on overall biology. Since the immune system is a key determinant of overall biological outcome, an altered biological state could be predicted by monitoring global changes in the immune profile. We postulate that every different exposure or a condition can generate a unique global immune profile in NHPs. Methods Changes in the global immune profile were evaluated in three different groups of rhesus macaques previously enrolled in dengue or malaria vaccine studies over six months after their last exposure. Naïve animals served as the baseline. Fresh blood samples were stained with various immune cell surface markers and analyzed by multi-color flow-cytometry to study immune cell dynamics in the peripheral blood. Serum cytokine profile in the pre-exposed animals were analyzed by mesoscale assay using a customized U-PLEX NHP biomarker panel of 12 cytokines/chemokines. Results Pre-exposed macaques showed altered dynamics in circulating cytokines and certain innate and adaptive immune cell subsets such as monocytes, HLA-DR+NKT cells, B cells and T cells. Some of these changes were transient, while some lasted for more than six months. Each group seemed to develop a global immune profile unique to their particular exposure. Conclusion Our data strongly suggest that re-used NHPs should be evaluated for long-term, overall immunological changes and randomly assigned to new studies to avoid study bias.https://peerj.com/articles/10955.pdfInnate and adaptive immunityRe-use of NHPs in researchInfectious diseasesCytokinesTrained immunityNon-human primates (NHPs)
spellingShingle François A. Bates
Elizabeth H. Duncan
Monika Simmons
Tanisha Robinson
Sridhar Samineni
Natasa Strbo
Eileen Villasante
Elke Bergmann-Leitner
Wathsala Wijayalath
Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
PeerJ
Innate and adaptive immunity
Re-use of NHPs in research
Infectious diseases
Cytokines
Trained immunity
Non-human primates (NHPs)
title Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
title_full Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
title_fullStr Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
title_full_unstemmed Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
title_short Exposure-related, global alterations in innate and adaptive immunity; a consideration for re-use of non-human primates in research
title_sort exposure related global alterations in innate and adaptive immunity a consideration for re use of non human primates in research
topic Innate and adaptive immunity
Re-use of NHPs in research
Infectious diseases
Cytokines
Trained immunity
Non-human primates (NHPs)
url https://peerj.com/articles/10955.pdf
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