Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity
Abstract Background Human-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life...
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ftdoajarticles:oai:doaj.org/article:e3d94b4a6fba415f85dabb98132ed839 2023-05-15T15:07:26+02:00 Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity Sai Majji Wathsala Wijayalath Soumya Shashikumar Teodor D. Brumeanu Sofia Casares 2018-03-01T00:00:00Z https://doi.org/10.1186/s12936-018-2264-y https://doaj.org/article/e3d94b4a6fba415f85dabb98132ed839 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2264-y https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2264-y 1475-2875 https://doaj.org/article/e3d94b4a6fba415f85dabb98132ed839 Malaria Journal, Vol 17, Iss 1, Pp 1-13 (2018) Humanized DRAGA mice Plasmodium falciparum Malaria Human T cells Antibodies Chloroquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2264-y 2022-12-31T05:17:54Z Abstract Background Human-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life cycle of Plasmodium falciparum. Herein, the DRAGA mice were investigated for immune responses following immunization with live P. falciparum sporozoites under chloroquine chemoprophylaxis (CPS-CQ), an immunization approach that showed in human trials to confer pre-erythrocytic immunity. Results The CPS-CQ immunized DRAGA mice (i) elicited human CD4 and CD8 T cell responses to antigens expressed by P. falciparum sporozoites (Pfspz) and by the infected-red blood cells (iRBC). The Pfspz-specific human T cell responses were found to be systemic (spleen and liver), whereas the iRBCs-specific human T cell responses were more localized to the liver, (ii) elicited stronger antibody responses to the Pfspz than to the iRBCs, and (iii) they were protected against challenge with infectious Pfspz but not against challenge with iRBCs. Conclusions The DRAGA mice represent a new pre-clinical model to investigate the immunogenicity and protective efficacy of P. falciparum malaria vaccine candidates. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Draga ENVELOPE(7.900,7.900,63.004,63.004) Malaria Journal 17 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Humanized DRAGA mice Plasmodium falciparum Malaria Human T cells Antibodies Chloroquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Humanized DRAGA mice Plasmodium falciparum Malaria Human T cells Antibodies Chloroquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Sai Majji Wathsala Wijayalath Soumya Shashikumar Teodor D. Brumeanu Sofia Casares Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
topic_facet |
Humanized DRAGA mice Plasmodium falciparum Malaria Human T cells Antibodies Chloroquine Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Human-immune-system humanized mouse models can bridge the gap between humans and conventional mice for testing human vaccines. The HLA-expressing humanized DRAGA (HLA-A2.HLA-DR4.Rag1KO.IL2RγcKO.NOD) mice reconstitute a functional human-immune-system and sustain the complete life cycle of Plasmodium falciparum. Herein, the DRAGA mice were investigated for immune responses following immunization with live P. falciparum sporozoites under chloroquine chemoprophylaxis (CPS-CQ), an immunization approach that showed in human trials to confer pre-erythrocytic immunity. Results The CPS-CQ immunized DRAGA mice (i) elicited human CD4 and CD8 T cell responses to antigens expressed by P. falciparum sporozoites (Pfspz) and by the infected-red blood cells (iRBC). The Pfspz-specific human T cell responses were found to be systemic (spleen and liver), whereas the iRBCs-specific human T cell responses were more localized to the liver, (ii) elicited stronger antibody responses to the Pfspz than to the iRBCs, and (iii) they were protected against challenge with infectious Pfspz but not against challenge with iRBCs. Conclusions The DRAGA mice represent a new pre-clinical model to investigate the immunogenicity and protective efficacy of P. falciparum malaria vaccine candidates. |
format |
Article in Journal/Newspaper |
author |
Sai Majji Wathsala Wijayalath Soumya Shashikumar Teodor D. Brumeanu Sofia Casares |
author_facet |
Sai Majji Wathsala Wijayalath Soumya Shashikumar Teodor D. Brumeanu Sofia Casares |
author_sort |
Sai Majji |
title |
Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
title_short |
Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
title_full |
Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
title_fullStr |
Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
title_full_unstemmed |
Humanized DRAGA mice immunized with Plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
title_sort |
humanized draga mice immunized with plasmodium falciparum sporozoites and chloroquine elicit protective pre-erythrocytic immunity |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2264-y https://doaj.org/article/e3d94b4a6fba415f85dabb98132ed839 |
long_lat |
ENVELOPE(7.900,7.900,63.004,63.004) |
geographic |
Arctic Draga |
geographic_facet |
Arctic Draga |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-13 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2264-y https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2264-y 1475-2875 https://doaj.org/article/e3d94b4a6fba415f85dabb98132ed839 |
op_doi |
https://doi.org/10.1186/s12936-018-2264-y |
container_title |
Malaria Journal |
container_volume |
17 |
container_issue |
1 |
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1766338946851143680 |