Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites
Abstract Background Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines are the only candidate malaria vaccines that induce > 90% vaccine efficacy (VE) against controlled human malaria infection and the only malaria vaccines to have achieved reproducible VE against malaria in adults in Africa. T...
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ftdoajarticles:oai:doaj.org/article:4fbb2445f2d24adaba6081405b24db41 2023-05-15T15:14:36+02:00 Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites Sumana Chakravarty Melanie J. Shears Eric R. James Urvashi Rai Natasha KC Solomon Conteh Lynn E. Lambert Patrick E. Duffy Sean C. Murphy Stephen L. Hoffman 2022-08-01T00:00:00Z https://doi.org/10.1186/s12936-022-04261-z https://doaj.org/article/4fbb2445f2d24adaba6081405b24db41 EN eng BMC https://doi.org/10.1186/s12936-022-04261-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04261-z 1475-2875 https://doaj.org/article/4fbb2445f2d24adaba6081405b24db41 Malaria Journal, Vol 21, Iss 1, Pp 1-11 (2022) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2022 ftdoajarticles https://doi.org/10.1186/s12936-022-04261-z 2022-12-30T22:13:42Z Abstract Background Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines are the only candidate malaria vaccines that induce > 90% vaccine efficacy (VE) against controlled human malaria infection and the only malaria vaccines to have achieved reproducible VE against malaria in adults in Africa. The goal is to increase the impact and reduce the cost of PfSPZ vaccines by optimizing vaccine potency and manufacturing, which will benefit from identification of immunological responses contributing to protection in humans. Currently, there is no authentic animal challenge model for assessing P. falciparum malaria VE. Alternatively, Plasmodium knowlesi (Pk), which infects humans and non-human primates (NHPs) in nature, can be used to experimentally infect rhesus macaques (Macaca mulatta) to assess VE. Methods Sanaria has, therefore, produced purified, vialed, cryopreserved PkSPZ and conducted challenge studies in several naïve NHP cohorts. In the first cohort, groups of three rhesus macaques each received doses of 5 × 102, 2.5 × 103, 1.25 × 104 and 2.5 × 104 PkSPZ administered by direct venous inoculation. The infectivity of 1.5 × 103 PkSPZ cryopreserved with an altered method and of 1.5 × 103 PkSPZ cryopreserved for four years was tested in a second and third cohort of rhesus NHPs. The lastly, three pig-tailed macaques (Macaca nemestrina), a natural P. knowlesi host, were challenged with 2.5 × 103 PkSPZ cryopreserved six years earlier. Results In the first cohort, all 12 animals developed P. knowlesi parasitaemia by thick blood smear, and the time to positivity (prepatent period) followed a non-linear 4-parameter logistic sigmoidal model with a median of 11, 10, 8, and 7 days, respectively (r2 = 1). PkSPZ cryopreserved using a modified rapid-scalable method infected rhesus with a pre-patent period of 10 days, as did PkSPZ cryopreserved four years prior to infection, similar to the control group. Cryopreserved PkSPZ infected pig-tailed macaques with median time to positivity by thin smear, of 11 days. Conclusion This ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 21 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Sumana Chakravarty Melanie J. Shears Eric R. James Urvashi Rai Natasha KC Solomon Conteh Lynn E. Lambert Patrick E. Duffy Sean C. Murphy Stephen L. Hoffman Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Plasmodium falciparum (Pf) sporozoite (SPZ) vaccines are the only candidate malaria vaccines that induce > 90% vaccine efficacy (VE) against controlled human malaria infection and the only malaria vaccines to have achieved reproducible VE against malaria in adults in Africa. The goal is to increase the impact and reduce the cost of PfSPZ vaccines by optimizing vaccine potency and manufacturing, which will benefit from identification of immunological responses contributing to protection in humans. Currently, there is no authentic animal challenge model for assessing P. falciparum malaria VE. Alternatively, Plasmodium knowlesi (Pk), which infects humans and non-human primates (NHPs) in nature, can be used to experimentally infect rhesus macaques (Macaca mulatta) to assess VE. Methods Sanaria has, therefore, produced purified, vialed, cryopreserved PkSPZ and conducted challenge studies in several naïve NHP cohorts. In the first cohort, groups of three rhesus macaques each received doses of 5 × 102, 2.5 × 103, 1.25 × 104 and 2.5 × 104 PkSPZ administered by direct venous inoculation. The infectivity of 1.5 × 103 PkSPZ cryopreserved with an altered method and of 1.5 × 103 PkSPZ cryopreserved for four years was tested in a second and third cohort of rhesus NHPs. The lastly, three pig-tailed macaques (Macaca nemestrina), a natural P. knowlesi host, were challenged with 2.5 × 103 PkSPZ cryopreserved six years earlier. Results In the first cohort, all 12 animals developed P. knowlesi parasitaemia by thick blood smear, and the time to positivity (prepatent period) followed a non-linear 4-parameter logistic sigmoidal model with a median of 11, 10, 8, and 7 days, respectively (r2 = 1). PkSPZ cryopreserved using a modified rapid-scalable method infected rhesus with a pre-patent period of 10 days, as did PkSPZ cryopreserved four years prior to infection, similar to the control group. Cryopreserved PkSPZ infected pig-tailed macaques with median time to positivity by thin smear, of 11 days. Conclusion This ... |
format |
Article in Journal/Newspaper |
author |
Sumana Chakravarty Melanie J. Shears Eric R. James Urvashi Rai Natasha KC Solomon Conteh Lynn E. Lambert Patrick E. Duffy Sean C. Murphy Stephen L. Hoffman |
author_facet |
Sumana Chakravarty Melanie J. Shears Eric R. James Urvashi Rai Natasha KC Solomon Conteh Lynn E. Lambert Patrick E. Duffy Sean C. Murphy Stephen L. Hoffman |
author_sort |
Sumana Chakravarty |
title |
Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
title_short |
Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
title_full |
Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
title_fullStr |
Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
title_full_unstemmed |
Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites |
title_sort |
efficient infection of non-human primates with purified, cryopreserved plasmodium knowlesi sporozoites |
publisher |
BMC |
publishDate |
2022 |
url |
https://doi.org/10.1186/s12936-022-04261-z https://doaj.org/article/4fbb2445f2d24adaba6081405b24db41 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 21, Iss 1, Pp 1-11 (2022) |
op_relation |
https://doi.org/10.1186/s12936-022-04261-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04261-z 1475-2875 https://doaj.org/article/4fbb2445f2d24adaba6081405b24db41 |
op_doi |
https://doi.org/10.1186/s12936-022-04261-z |
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Malaria Journal |
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21 |
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1766345041941364736 |