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2. Stronger induction of trained immunity by mucosal BCG or MTBVAC vaccination compared to standard intradermal vaccination

Author

Vierboom, Michel P.M., Dijkman, Karin, Sombroek, Claudia C., Hofman, Sam O., Boot, Charelle, Vervenne, Richard A.W., Haanstra, Krista G., van der Sande, Maarten, van Emst, Liesbeth, Domínguez-Andrés, Jorge, Moorlag, Simone J.C.F.M., Kocken, Clemens H.M., Thole, Jelle, Rodríguez, Esteban, Puentes, Eugenia, Martens, Joost H.A., van Crevel, Reinout, Netea, Mihai G., Aguilo, Nacho, Martin, Carlos, and Verreck, Frank A.W.

Published
2021
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3. Variable BCG efficacy in rhesus populations: Pulmonary BCG provides protection where standard intra-dermal vaccination fails

Author

Verreck, Frank A.W., Tchilian, Elma Z., Vervenne, Richard A.W., Sombroek, Claudia C., Kondova, Ivanela, Eissen, Okke A., Sommandas, Vinod, van der Werff, Nicole M., Verschoor, Ernst, Braskamp, Gerco, Bakker, Jaco, Langermans, Jan A.M., Heidt, Peter J., Ottenhoff, Tom H.M., van Kralingen, Klaas W., Thomas, Alan W., Beverley, Peter C.L., and Kocken, Clemens H.M.

Published
2017
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4. Evaluation of heterologous prime-boost vaccination strategies using chimpanzee adenovirus and modified vaccinia virus for TB subunit vaccination in rhesus macaques

Author

Vierboom, Michel P. M., Chenine, Agnes L., Darrah, Patricia A., Vervenne, Richard A. W., Boot, Charelle, Hofman, Sam O., Sombroek, Claudia C., Dijkman, Karin, Khayum, Mohamed A., Stammes, Marieke A., Haanstra, Krista G., Hoffmann, Chantal, Schmitt, Doris, Silvestre, Nathalie, White, Alexander G., Borish, H. Jacob, Seder, Robert A., Ouaked, Nadia, Leung-Theung-Long, Stephane, Inchauspé, Geneviève, Anantha, Ravi, Limbach, Mary, Evans, Thomas G., Casimiro, Danilo, Lempicki, Maria, Laddy, Dominick J., Bonavia, Aurelio, and Verreck, Frank A. W.

Published
2020
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5. Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques

Author

Dijkman, Karin, Sombroek, Claudia C., Vervenne, Richard A. W., Hofman, Sam O., Boot, Charelle, Remarque, Edmond J., and Kocken, Clemens H. M.

Subjects
BCG -- Usage, Rhesus monkey -- Research -- Health aspects, Immune response -- Research, Tuberculosis -- Prevention -- Research, Immunoglobulin A, Vaccines, Immunoglobulins, Interleukins, Skin, Immunization, Wildlife conservation, Vaccination, Biological sciences, Health
Abstract

Tuberculosis (TB) remains the deadliest infectious disease.sup.1, and the widely used Bacillus Calmette-Guérin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance.sup.2,3. Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Therefore, assessment of new strategies in preclinical models to select the best candidate vaccines before clinical vaccine testing remains indispensable. We have previously established in rhesus macaques (Macaca mulatta) that pulmonary mucosal BCG delivery reduces TB disease where standard intradermal injection fails.sup.4,5. Here, we show that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and identify polyfunctional T-helper type 17 (T.sub.H17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity. These findings warrant further research into mucosal immunization strategies and their translation to clinical application to more effectively prevent the spread of TB. Delivery of the Bacillus Calmette-Guérin vaccine into the lungs but not the skin of rhesus macaques protects animals from infection with Mycobacterium tuberculosis, suggesting that immune responses elicited locally may be required for vaccine efficacy., Author(s): Karin Dijkman [sup.1] , Claudia C. Sombroek [sup.1] , Richard A. W. Vervenne [sup.1] , Sam O. Hofman [sup.1] , Charelle Boot [sup.1] , Edmond J. Remarque [sup.1] , [...]

Published
2019
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7. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, Verstrepen, Babs E, Sub Theoretical Biology, AISS LAS/3'R Centre ULS, and Theoretical Biology and Bioinformatics

Subjects
NHPs, Infectious Diseases, SARS-CoV-2, Virology, COVID-19, Animal models, Non-human primates
Abstract

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Published
2021

10. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Böszörményi, Kinga P., primary, Stammes, Marieke A., additional, Fagrouch, Zahra C., additional, Kiemenyi-Kayere, Gwendoline, additional, Niphuis, Henk, additional, Mortier, Daniella, additional, van Driel, Nikki, additional, Nieuwenhuis, Ivonne, additional, Vervenne, Richard A. W., additional, Haaksma, Tom, additional, Ouwerling, Boudewijn, additional, Adema, Deborah, additional, Acar, Roja Fidel, additional, Zuiderwijk-Sick, Ella, additional, Meijer, Lisette, additional, Mooij, Petra, additional, Remarque, Ed J., additional, Oostermeijer, Herman, additional, Koopman, Gerrit, additional, Hoste, Alexis C. R., additional, Sastre, Patricia, additional, Haagmans, Bart L., additional, Bontrop, Ronald E., additional, Langermans, Jan A. M., additional, Bogers, Willy M., additional, Kondova, Ivanela, additional, Verschoor, Ernst J., additional, and Verstrepen, Babs E., additional

Published
2021
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11. Recommendations for Standardizing Thorax PET-CT in Non-Human Primates by Recent Experience from Macaque Studies

Author

Stammes, Marieke A, Bakker, Jaco, Vervenne, Richard A W, Zijlmans, Dian G M, van Geest, Leo, Vierboom, Michel P M, Langermans, Jan A M, Verreck, Frank A W, Stammes, Marieke A, Bakker, Jaco, Vervenne, Richard A W, Zijlmans, Dian G M, van Geest, Leo, Vierboom, Michel P M, Langermans, Jan A M, and Verreck, Frank A W

Abstract

Despite the possibilities of routine clinical measures and assays on readily accessible bio-samples, it is not always essential in animals to investigate the dynamics of disease longitudinally. In this regard, minimally invasive imaging methods provide powerful tools in preclinical research. They can contribute to the ethical principle of gathering as much relevant information per animal as possible. Besides, with an obvious parallel to clinical diagnostic practice, such imaging platforms are potent and valuable instruments leading to a more refined use of animals from a welfare perspective. Non-human primates comprise highly relevant species for preclinical research to enhance our understanding of disease mechanisms and/or the development of improved prophylactic or therapeutic regimen for various human diseases. In this paper, we describe parameters that critically affect the quality of integrated positron emission tomography and computed tomography (PET-CT) in non-human primates. Lessons learned are exemplified by results from imaging experimental infectious respiratory disease in macaques; specifically tuberculosis, influenza, and SARS-CoV-2 infection. We focus on the thorax and use of 18F-fluorodeoxyglucose as a PET tracer. Recommendations are provided to guide various stages of PET-CT-supported research in non-human primates, from animal selection, scan preparation, and operation, to processing and analysis of imaging data.

Published
2021

12. The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Author

Sub Theoretical Biology, AISS LAS/3'R Centre ULS, Theoretical Biology and Bioinformatics, Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, Verstrepen, Babs E, Sub Theoretical Biology, AISS LAS/3'R Centre ULS, Theoretical Biology and Bioinformatics, Böszörményi, Kinga, Stammes, Marieke, Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, Driel, Nikki van, Nieuwenhuis, Ivonne, Vervenne, Richard A. W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Hoste, Alexis C. R., Sastre, Patricia, Haagmans, Bart, Bontrop, Ronald E., Langermans, Jan, Bogers, Willy, Kondova, Ivanela, Verschoor, Ernst, and Verstrepen, Babs E

Published
2021

13. Recommendations for Standardizing Thorax PET-CT in Non-Human Primates by Recent Experience from Macaque Studies

Author

AISS LAS/3'R Centre ULS, Stammes, Marieke A, Bakker, Jaco, Vervenne, Richard A W, Zijlmans, Dian G M, van Geest, Leo, Vierboom, Michel P M, Langermans, Jan A M, Verreck, Frank A W, AISS LAS/3'R Centre ULS, Stammes, Marieke A, Bakker, Jaco, Vervenne, Richard A W, Zijlmans, Dian G M, van Geest, Leo, Vierboom, Michel P M, Langermans, Jan A M, and Verreck, Frank A W

Published
2021

14. The post-acute phase of sars-cov-2 infection in two macaque species is associated with signs of ongoing virus replication and pathology in pulmonary and extrapulmonary tissues

Author

Böszörményi, Kinga P., Stammes, Marieke A., Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, van Driel, Nikki, Nieuwenhuis, Ivonne, Vervenne, Richard A.W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Koopman, Gerrit, Hoste, Alexis C.R., Sastre, Patricia, Haagmans, Bart L., Bontrop, Ronald E., Langermans, Jan A.M., Bogers, Willy M., Kondova, Ivanela, Verschoor, Ernst J., Verstrepen, Babs E., Böszörményi, Kinga P., Stammes, Marieke A., Fagrouch, Zahra C., Kiemenyi-Kayere, Gwendoline, Niphuis, Henk, Mortier, Daniella, van Driel, Nikki, Nieuwenhuis, Ivonne, Vervenne, Richard A.W., Haaksma, Tom, Ouwerling, Boudewijn, Adema, Deborah, Acar, Roja Fidel, Zuiderwijk-Sick, Ella, Meijer, Lisette, Mooij, Petra, Remarque, Ed J., Oostermeijer, Herman, Koopman, Gerrit, Hoste, Alexis C.R., Sastre, Patricia, Haagmans, Bart L., Bontrop, Ronald E., Langermans, Jan A.M., Bogers, Willy M., Kondova, Ivanela, Verschoor, Ernst J., and Verstrepen, Babs E.

Abstract

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.

Published
2021

16. The post-acute phase of SARS-CoV-2 infection in two macaques species is associated with signs of ongoing virus replication and pathology in pulmonary and extrapulmonary tissues

Author

Böszörményi, Kinga P., primary, Stammes, Marieke A., additional, Fagrouch, Zahra C., additional, Kiemenyi-Kayere, Gwendoline, additional, Niphuis, Henk, additional, Mortier, Daniella, additional, van Driel, Nikki, additional, Nieuwenhuis, Ivonne, additional, Vervenne, Richard A. W., additional, Haaksma, Tom, additional, Ouwerling, Boudewijn, additional, Adema, Deborah, additional, Acar, Roja Fidel, additional, Zuiderwijk-Sick, Ella, additional, Meijer, Lisette, additional, Mooij, Petra, additional, Remarque, Ed J., additional, Oostermeijer, Herman, additional, Koopman, Gerrit, additional, Hoste, Alexis C. R., additional, Sastre, Patricia, additional, Haagmans, Bart L., additional, Bontrop, Ronald E., additional, Langermans, Jan A.M., additional, Bogers, Willy M., additional, Kondova, Ivanela, additional, Verschoor, Ernst J., additional, and Verstrepen, Babs E., additional

Published
2020
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17. Respiratory Immunization With a Whole Cell Inactivated Vaccine Induces Functional Mucosal Immunoglobulins Against Tuberculosis in Mice and Non-human Primates

Author

Aguilo, Nacho, primary, Uranga, Santiago, additional, Mata, Elena, additional, Tarancon, Raquel, additional, Gómez, Ana Belén, additional, Marinova, Dessislava, additional, Otal, Isabel, additional, Monzón, Marta, additional, Badiola, Juan, additional, Montenegro, Dolores, additional, Puentes, Eugenia, additional, Rodríguez, Esteban, additional, Vervenne, Richard A. W., additional, Sombroek, Claudia C., additional, Verreck, Frank A. W., additional, and Martín, Carlos, additional

Published
2020
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22. Disparate Tuberculosis Disease Development in Macaque Species Is Associated With Innate Immunity

Author

Dijkman, Karin, primary, Vervenne, Richard A. W., additional, Sombroek, Claudia C., additional, Boot, Charelle, additional, Hofman, Sam O., additional, van Meijgaarden, Krista E., additional, Ottenhoff, Tom H. M., additional, Kocken, Clemens H. M., additional, Haanstra, Krista G., additional, Vierboom, Michel P. M., additional, and Verreck, Frank A. W., additional

Published
2019
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23. Divergent effect of bacillus Calmette--Guerin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: Implications for primate models in tuberculosis vaccine research

Author

Langermans, Jan A. M., Andersen, Peter, van Soolingen, Dick, Vervenne, Richard A. W., Frost, Patrice A., van der Laan, Tridia, van Pinxteren, Laurens A. H., van den Hombergh, Jan, Kroon, Saskia, Peekel, Inge, Florquin, Sandrine, and Thomas, Alan W.

Subjects
Mycobacterium tuberculosis -- Research, Macaques -- Research, BCG vaccines -- Research, Tuberculosis -- Prevention, Science and technology
Abstract

Despite the widespread use of bacillus Calmette--Guerin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease very similar to humans, they have potential to provide important information in addition to small animal models. To assess the relative merits of rhesus and cynomolgus monkeys as screens for tuberculosis vaccines, we compared the efficacy of bacillus Calmette--Guerin vaccination and the course of infection in both species. Unvaccinated rhesus and cynomolgus monkeys both developed progressive disease with high levels of C-reactive protein, M. tuberculosis-specific IgG, and extensive pathology including cavitation and caseous necrosis. Bacillus Calmette--Guerin vaccination protected cynomolgus almost completely toward the development of pathology, reflected in a striking 2-log reduction in viable bacteria in the lungs compared with nonvaccinated animals. Rhesus, on the other hand, were not protected efficiently by the bacillus Calmette--Guerin. The vaccinated animals developed substantial pathology and had negligible reductions of colony-forming units in the lungs. Comparative studies in these closely related species are likely to provide insight into mechanisms involved in protection against tuberculosis.

Published
2001

24. Correction: MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques

Author

Verreck, Frank A. W., primary, Vervenne, Richard A. W., additional, Kondova, Ivanela, additional, van Kralingen, Klaas W., additional, Remarque, Edmond J., additional, Braskamp, Gerco, additional, van der Werff, Nicole M., additional, Kersbergen, Ariena, additional, Ottenhoff, Tom H. M., additional, Heidt, Peter J., additional, Gilbert, Sarah C., additional, Gicquel, Brigitte, additional, Hill, Adrian V. S., additional, Martin, Carlos, additional, McShane, Helen, additional, and Thomas, Alan W., additional

Published
2011
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25. MVA.85A Boosting of BCG and an Attenuated, phoP Deficient M. tuberculosis Vaccine Both Show Protective Efficacy Against Tuberculosis in Rhesus Macaques

Author

Verreck, Frank A. W., primary, Vervenne, Richard A. W., additional, Kondova, Ivanela, additional, van Kralingen, Klaas W., additional, Remarque, Edmond J., additional, Braskamp, Gerco, additional, van der Werff, Nicole M., additional, Kersbergen, Ariena, additional, Ottenhoff, Tom H. M., additional, Heidt, Peter J., additional, Gilbert, Sarah C., additional, Gicquel, Brigitte, additional, Hill, Adrian V. S., additional, Martin, Carlos, additional, McShane, Helen, additional, and Thomas, Alan W., additional

Published
2009
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29. Juvenile Rhesus Monkeys Have Lower Type 2 Cytokine Responses than Adults after Primary Infection withSchistosoma mansoni

Author

Fallon, Padraic G., primary, Gibbons, Jason, additional, Vervenne, Richard A., additional, Richardson, Emma J., additional, Fulford, Anthony J. C., additional, Kiarie, Simon, additional, Sturrock, Robert F., additional, Coulson, Patricia S., additional, Deelder, Andre M., additional, Langermans, Jan A. M., additional, Thomas, Alan W., additional, and Dunne, David W., additional

Published
2003
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35. Transfected Plasmodium knowlesiProduces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites

Author

Ozwara, Hastings, Langermans, Jan A. M., Kocken, Clemens H. M., van der Wel, Annemarie, van der Meide, Peter H., Vervenne, Richard A. W., Mwenda, Jason M., and Thomas, Alan W.

Abstract

ABSTRACTTransgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-γ) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesiparasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-γ under the control of the heterologous P. bergheiapical membrane antigen 1 promoter, produced bioactive IFN-γ in a developmentally regulated manner. IFN-γ expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-γ was shown through inhibition of virus cytopathic effect and confirmed by using M. mulattaperipheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.

Published
2003
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36. TB diagnosis in non-human primates: comparison of two interferon-gamma assays and the skin test for identification of Mycobacterium tuberculosis infection.

Author

Vervenne RA, Jones SL, van Soolingen D, van der Laan T, Andersen P, Heidt PJ, Thomas AW, and Langermans JA

Subjects
Animals, Enzyme-Linked Immunosorbent Assay methods, Enzyme-Linked Immunosorbent Assay veterinary, Female, Interferon-gamma blood, Macaca fascicularis, Macaca mulatta, Male, Monkey Diseases immunology, Reproducibility of Results, Tuberculin Test veterinary, Tuberculosis immunology, Tuberculosis microbiology, Interferon-gamma immunology, Monkey Diseases diagnosis, Monkey Diseases microbiology, Mycobacterium tuberculosis, Tuberculosis diagnosis, Tuberculosis veterinary
Abstract

In general non-human primates are highly susceptible to infections with Mycobacterium tuberculosis which therefore presents an explosive health threat to colonies. To screen for M. tuberculosis infections in non-human primates, the skin test is routinely used. However, the reliability of this test in primates is debatable. The aim of this study was to compare relatively easy in vitro diagnostic tests for TB with the skin test for detection of a tuberculosis (TB) infection. Two in vitro assays, a whole blood interferon-gamma (WB IFN-gamma) assay and in vitro stimulation of isolated lymphocytes (PBMC IFN-gamma) were evaluated during both experimental TB infections in macaques as well as during an outbreak of TB in a macaque quarantine facility. The WB IFN-gamma assay was also evaluated on healthy old and new world monkeys. Our results show that both in vitro assays detected TB infection in macaques. All experimentally infected animals showed TB-specific responses in both assays. In contrast, several TB animals were not diagnosed TB positive using the skin test. In addition, during the outbreak in the quarantine facility one animal was not detected using the routinely used skin test, but it showed strong positive responses in the WB assay. In conclusion, the in vitro assays are a valuable tool for screening non-human primates for TB infection, especially because the assays cause relatively less stress for the animals compared to the skin test and give reproducible and reliable results.

Published
2004
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