Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model

Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to s...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Tejram eSahu [verfasserIn] Lynn eLambert [verfasserIn] Jessica eHerrod [verfasserIn] Solomon eConteh [verfasserIn] Sachy eOrr-Gonzalez [verfasserIn] Dariyen eCarter [verfasserIn] Patrick E Duffy [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Chloroquine Plasmodium Liver-stage CVac Prepatent

Übergeordnetes Werk:	In: Frontiers in Microbiology - Frontiers Media S.A., 2011, 6(2015)
Übergeordnetes Werk:	volume:6 ; year:2015

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmicb.2015.00283

Katalog-ID:	DOAJ023625767

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allfields	10.3389/fmicb.2015.00283 doi (DE-627)DOAJ023625767 (DE-599)DOAJ99c1973334f4465cb55f91fadf6e3e60 DE-627 ger DE-627 rakwb eng QR1-502 Tejram eSahu verfasserin aut Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. Chloroquine Plasmodium Liver-stage CVac Prepatent Microbiology Lynn eLambert verfasserin aut Jessica eHerrod verfasserin aut Solomon eConteh verfasserin aut Sachy eOrr-Gonzalez verfasserin aut Dariyen eCarter verfasserin aut Patrick E Duffy verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 6(2015) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:6 year:2015 https://doi.org/10.3389/fmicb.2015.00283 kostenfrei https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2015
spelling	10.3389/fmicb.2015.00283 doi (DE-627)DOAJ023625767 (DE-599)DOAJ99c1973334f4465cb55f91fadf6e3e60 DE-627 ger DE-627 rakwb eng QR1-502 Tejram eSahu verfasserin aut Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. Chloroquine Plasmodium Liver-stage CVac Prepatent Microbiology Lynn eLambert verfasserin aut Jessica eHerrod verfasserin aut Solomon eConteh verfasserin aut Sachy eOrr-Gonzalez verfasserin aut Dariyen eCarter verfasserin aut Patrick E Duffy verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 6(2015) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:6 year:2015 https://doi.org/10.3389/fmicb.2015.00283 kostenfrei https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2015
allfields_unstemmed	10.3389/fmicb.2015.00283 doi (DE-627)DOAJ023625767 (DE-599)DOAJ99c1973334f4465cb55f91fadf6e3e60 DE-627 ger DE-627 rakwb eng QR1-502 Tejram eSahu verfasserin aut Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. Chloroquine Plasmodium Liver-stage CVac Prepatent Microbiology Lynn eLambert verfasserin aut Jessica eHerrod verfasserin aut Solomon eConteh verfasserin aut Sachy eOrr-Gonzalez verfasserin aut Dariyen eCarter verfasserin aut Patrick E Duffy verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 6(2015) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:6 year:2015 https://doi.org/10.3389/fmicb.2015.00283 kostenfrei https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2015
allfieldsGer	10.3389/fmicb.2015.00283 doi (DE-627)DOAJ023625767 (DE-599)DOAJ99c1973334f4465cb55f91fadf6e3e60 DE-627 ger DE-627 rakwb eng QR1-502 Tejram eSahu verfasserin aut Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. Chloroquine Plasmodium Liver-stage CVac Prepatent Microbiology Lynn eLambert verfasserin aut Jessica eHerrod verfasserin aut Solomon eConteh verfasserin aut Sachy eOrr-Gonzalez verfasserin aut Dariyen eCarter verfasserin aut Patrick E Duffy verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 6(2015) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:6 year:2015 https://doi.org/10.3389/fmicb.2015.00283 kostenfrei https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2015
allfieldsSound	10.3389/fmicb.2015.00283 doi (DE-627)DOAJ023625767 (DE-599)DOAJ99c1973334f4465cb55f91fadf6e3e60 DE-627 ger DE-627 rakwb eng QR1-502 Tejram eSahu verfasserin aut Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development. Chloroquine Plasmodium Liver-stage CVac Prepatent Microbiology Lynn eLambert verfasserin aut Jessica eHerrod verfasserin aut Solomon eConteh verfasserin aut Sachy eOrr-Gonzalez verfasserin aut Dariyen eCarter verfasserin aut Patrick E Duffy verfasserin aut In Frontiers in Microbiology Frontiers Media S.A., 2011 6(2015) (DE-627)642889384 (DE-600)2587354-4 1664302X nnns volume:6 year:2015 https://doi.org/10.3389/fmicb.2015.00283 kostenfrei https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full kostenfrei https://doaj.org/toc/1664-302X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2015
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topic_title	QR1-502 Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model Chloroquine Plasmodium Liver-stage CVac Prepatent
topic	misc QR1-502 misc Chloroquine misc Plasmodium misc Liver-stage misc CVac misc Prepatent misc Microbiology
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title	Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model
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title_full	Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model
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title_sort	chloroquine neither eliminates liver stage parasites nor delays their development in a murine chemoprophylaxis vaccination model
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title_auth	Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model
abstract	Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development.
abstractGer	Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development.
abstract_unstemmed	Chemoprophylaxis Vaccination (CVac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites under drug cover. CVac using the drug chloroquine (CQ) induces pre-erythrocytic immunity in humans that includes antibody to sporozoites and T-cell responses to liver stage parasites. The mechanism by which CVac with CQ induces strong protective immunity is not understood as untreated infections do not confer protection. CQ kills blood stage parasites, but its effect on liver stage parasites is poorly studied. Here we hypothesized that CQ may prolong or perturb liver stage development of Plasmodium, as a potential explanation for enhanced pre-erythrocytic immune responses. Balb/c mice with or without CQ prophylaxis were infected with sporozoite forms of a luciferase-expressing rodent parasite, Plasmodium yoelii-Luc (Py-Luc). Mice that received primaquine (PQ), a drug that kills liver stage parasites, served as a positive control of drug effect. Parasite burden in liver was measured both by bioluminescence and by qRT-PCR quantification of parasite transcript. Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. Further investigations into the mechanism of CQ-induced protection after CVac are required, and may give insights relevant to drug and vaccine development.
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title_short	Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model
url	https://doi.org/10.3389/fmicb.2015.00283 https://doaj.org/article/99c1973334f4465cb55f91fadf6e3e60 http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00283/full https://doaj.org/toc/1664-302X
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Time to appearance of parasites in the blood was monitored by microscopic analysis of Giemsa-stained thick and thin blood smears. The parasite load in livers of CQ-treated and untreated mice did not significantly differ at any of the time points studied. Parasites appeared in the blood smears of both CQ-treated and untreated mice 3 days after infection. Taken together, our findings confirm that CQ neither eliminates liver stage parasites nor delays their development. 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Chloroquine neither eliminates liver stage parasites nor delays their development in a murine Chemoprophylaxis Vaccination model

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