Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy
Abstract Background The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy...
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ftdoajarticles:oai:doaj.org/article:7fa67b33fb51451aa7f82bdbb192e90e 2023-05-15T15:15:07+02:00 Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy Bergmann-Leitner Elke S Leitner Wolfgang W Angov Evelina 2010-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-145 https://doaj.org/article/7fa67b33fb51451aa7f82bdbb192e90e EN eng BMC http://www.malariajournal.com/content/9/1/145 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-145 1475-2875 https://doaj.org/article/7fa67b33fb51451aa7f82bdbb192e90e Malaria Journal, Vol 9, Iss 1, p 145 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-145 2022-12-31T08:49:35Z Abstract Background The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of Plasmodium berghei and Plasmodium yoelii , parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the P. berghei model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV) delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, i.e ., the subcutaneous challenge. Methods Mice were infected with P. berghei sporozoites by intravenous (tail vein) injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun. Results Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was optimized. This approach, too, yields reliable challenge results, ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
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 Bergmann-Leitner Elke S Leitner Wolfgang W Angov Evelina Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of Plasmodium berghei and Plasmodium yoelii , parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the P. berghei model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV) delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, i.e ., the subcutaneous challenge. Methods Mice were infected with P. berghei sporozoites by intravenous (tail vein) injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun. Results Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was optimized. This approach, too, yields reliable challenge results, ... |
format |
Article in Journal/Newspaper |
author |
Bergmann-Leitner Elke S Leitner Wolfgang W Angov Evelina |
author_facet |
Bergmann-Leitner Elke S Leitner Wolfgang W Angov Evelina |
author_sort |
Bergmann-Leitner Elke S |
title |
Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
title_short |
Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
title_full |
Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
title_fullStr |
Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
title_full_unstemmed |
Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
title_sort |
comparison of plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-145 https://doaj.org/article/7fa67b33fb51451aa7f82bdbb192e90e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 145 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/145 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-145 1475-2875 https://doaj.org/article/7fa67b33fb51451aa7f82bdbb192e90e |
op_doi |
https://doi.org/10.1186/1475-2875-9-145 |
container_title |
Malaria Journal |
container_volume |
9 |
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1 |
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1766345506416492544 |