Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein
Abstract Background New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates and speed development, it is essential to stan...
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ftdoajarticles:oai:doaj.org/article:4b5eb85f1d8e48149087791ff171d018 2023-05-15T15:13:28+02:00 Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein Rama Raghunandan Bryan T. Mayer Yevel Flores-Garcia Monica W. Gerber Raphael Gottardo Hugo Jhun Sonia M. Herrera Daniel W. Perez-Ramos Emily Locke C. Richter King Fidel Zavala 2020-03-01T00:00:00Z https://doi.org/10.1186/s12936-020-03181-0 https://doaj.org/article/4b5eb85f1d8e48149087791ff171d018 EN eng BMC http://link.springer.com/article/10.1186/s12936-020-03181-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03181-0 1475-2875 https://doaj.org/article/4b5eb85f1d8e48149087791ff171d018 Malaria Journal, Vol 19, Iss 1, Pp 1-15 (2020) Malaria Transgenic parasite Bioluminescence Monoclonal antibodies Functional activity Circumsporozoite protein (CSP) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2020 ftdoajarticles https://doi.org/10.1186/s12936-020-03181-0 2022-12-31T03:53:12Z Abstract Background New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates and speed development, it is essential to standardize preclinical assays to measure the potency of such interventions in animal models. Methods Two assay configurations were studied using transgenic Plasmodium berghei expressing Plasmodium falciparum full-length circumsporozoite protein. The assays measured (1) reduction in parasite infection of the liver (liver burden) following an intravenous (i.v) administration of sporozoites and (2) protection from parasitaemia following mosquito bite challenge. Two human CSP mAbs, AB311 and AB317, were compared for their ability to inhibit infection. Multiple independent experiments were conducted to define assay variability and resultant impact on the ability to discriminate differences in mAb functional activity. Results Overall, the assays produced highly consistent results in that all individual experiments showed greater functional activity for AB317 compared to AB311 as calculated by the dose required for 50% inhibition (ID50) as well as the serum concentration required for 50% inhibition (IC50). The data were then used to model experimental designs with adequate statistical power to rigorously screen, compare, and rank order novel anti-CSP mAbs. Conclusion The results indicate that in vivo assays described here can provide reliable information for comparing the functional activity of mAbs. The results also provide guidance regarding selection of the appropriate experimental design, dose selection, and group sizes. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 19 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Transgenic parasite Bioluminescence Monoclonal antibodies Functional activity Circumsporozoite protein (CSP) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Transgenic parasite Bioluminescence Monoclonal antibodies Functional activity Circumsporozoite protein (CSP) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Rama Raghunandan Bryan T. Mayer Yevel Flores-Garcia Monica W. Gerber Raphael Gottardo Hugo Jhun Sonia M. Herrera Daniel W. Perez-Ramos Emily Locke C. Richter King Fidel Zavala Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
topic_facet |
Malaria Transgenic parasite Bioluminescence Monoclonal antibodies Functional activity Circumsporozoite protein (CSP) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates and speed development, it is essential to standardize preclinical assays to measure the potency of such interventions in animal models. Methods Two assay configurations were studied using transgenic Plasmodium berghei expressing Plasmodium falciparum full-length circumsporozoite protein. The assays measured (1) reduction in parasite infection of the liver (liver burden) following an intravenous (i.v) administration of sporozoites and (2) protection from parasitaemia following mosquito bite challenge. Two human CSP mAbs, AB311 and AB317, were compared for their ability to inhibit infection. Multiple independent experiments were conducted to define assay variability and resultant impact on the ability to discriminate differences in mAb functional activity. Results Overall, the assays produced highly consistent results in that all individual experiments showed greater functional activity for AB317 compared to AB311 as calculated by the dose required for 50% inhibition (ID50) as well as the serum concentration required for 50% inhibition (IC50). The data were then used to model experimental designs with adequate statistical power to rigorously screen, compare, and rank order novel anti-CSP mAbs. Conclusion The results indicate that in vivo assays described here can provide reliable information for comparing the functional activity of mAbs. The results also provide guidance regarding selection of the appropriate experimental design, dose selection, and group sizes. |
format |
Article in Journal/Newspaper |
author |
Rama Raghunandan Bryan T. Mayer Yevel Flores-Garcia Monica W. Gerber Raphael Gottardo Hugo Jhun Sonia M. Herrera Daniel W. Perez-Ramos Emily Locke C. Richter King Fidel Zavala |
author_facet |
Rama Raghunandan Bryan T. Mayer Yevel Flores-Garcia Monica W. Gerber Raphael Gottardo Hugo Jhun Sonia M. Herrera Daniel W. Perez-Ramos Emily Locke C. Richter King Fidel Zavala |
author_sort |
Rama Raghunandan |
title |
Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
title_short |
Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
title_full |
Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
title_fullStr |
Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
title_full_unstemmed |
Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein |
title_sort |
characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to plasmodium falciparum circumsporozoite protein |
publisher |
BMC |
publishDate |
2020 |
url |
https://doi.org/10.1186/s12936-020-03181-0 https://doaj.org/article/4b5eb85f1d8e48149087791ff171d018 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 19, Iss 1, Pp 1-15 (2020) |
op_relation |
http://link.springer.com/article/10.1186/s12936-020-03181-0 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03181-0 1475-2875 https://doaj.org/article/4b5eb85f1d8e48149087791ff171d018 |
op_doi |
https://doi.org/10.1186/s12936-020-03181-0 |
container_title |
Malaria Journal |
container_volume |
19 |
container_issue |
1 |
_version_ |
1766344024971542528 |