Abstract:
:A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria species Plasmodium knowlesi including two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen 1 (PkAMA1) and merozoite surface protein 1 (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100 P. knowlesi sporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Rogers WO,Baird JK,Kumar A,Tine JA,Weiss W,Aguiar JC,Gowda K,Gwadz R,Kumar S,Gold M,Hoffman SLdoi
10.1128/iai.69.9.5565-5572.2001keywords:
subject
Has Abstractpub_date
2001-09-01 00:00:00pages
5565-72issue
9eissn
0019-9567issn
1098-5522journal_volume
69pub_type
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journal_title:Infection and immunity
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doi:10.1128/IAI.57.8.2542-2546.1989
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.11.1.42-51.1975
更新日期:1975-01-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.18.1.41-45.1977
更新日期:1977-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.7.3.380-385.1973
更新日期:1973-03-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.53.3.693-696.1986
更新日期:1986-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01743-07
更新日期:2008-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2001-12-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.31.3.1177-1183.1981
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1973-09-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00425-09
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journal_title:Infection and immunity
pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.4.1.20-22.1971
更新日期:1971-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1996-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2005-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1994-11-01 00:00:00