Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination

被引:8
作者
Mueller, Katja [1 ,2 ]
Gibbins, Matthew P. [3 ,6 ]
Roberts, Mark [3 ]
Reyes-Sandoval, Arturo [4 ,7 ]
Hill, Adrian V. S. [4 ]
Draper, Simon J. [4 ]
Matuschewski, Kai [1 ,2 ]
Silvie, Olivier [5 ]
Hafalla, Julius Clemence R. [3 ]
机构
[1] Max Planck Inst Infect Biol, Parasitol Unit, Berlin, Germany
[2] Humboldt Univ, Inst Biol, Dept Mol Parasitol, Berlin, Germany
[3] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect Biol, London, England
[4] Univ Oxford, Jenner Inst, Oxford, England
[5] Sorbonne Univ, CIMI Paris, CNRS, Ctr Immunol & Malad Infect, Paris, France
[6] Univ Glasgow, Inst Infect Immun & Inflammat, Wellcome Ctr Integrat Parasitol, Glasgow, Lanark, Scotland
[7] Inst Politecn Nacl, IPN, Unidad Adolfo Lopez Mateos, Av Luis Enrique Erro S-N, Mexico City, DF, Mexico
基金
英国国家替代、减少和改良动物研究中心; 英国惠康基金;
关键词
immunogenicity; malaria; Plasmodium; pre‐ erythrocytic; protective efficacy; CD8(+) T-CELLS; PLASMODIUM-BERGHEI; CIRCUMSPOROZOITE PROTEIN; PROTECTIVE EFFICACY; IMMUNIZATION; IMMUNITY; SPOROZOITES; RECOGNIZE; VACCINES; MICE;
D O I
10.15252/emmm.202013390
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Immunogenicity is considered one important criterion for progression of candidate vaccines to further clinical evaluation. We tested this assumption in an infection and vaccination model for malaria pre-erythrocytic stages. We engineered Plasmodium berghei parasites that harbour a well-characterised epitope for stimulation of CD8(+) T cells, either as an antigen in the sporozoite surface-expressed circumsporozoite protein or the parasitophorous vacuole membrane associated protein upregulated in sporozoites 4 (UIS4) expressed in exo-erythrocytic forms (EEFs). We show that the antigen origin results in profound differences in immunogenicity with a sporozoite antigen eliciting robust, superior antigen-specific CD8(+) T-cell responses, whilst an EEF antigen evokes poor responses. Despite their contrasting immunogenic properties, both sporozoite and EEF antigens gain access to antigen presentation pathways in hepatocytes, as recognition and targeting by vaccine-induced effector CD8(+) T cells results in high levels of protection when targeting either antigen. Our study is the first demonstration that poorly immunogenic EEF antigens do not preclude their susceptibility to antigen-specific CD8(+) T-cell killing, which has wide-ranging implications on antigen prioritisation for next-generation pre-erythrocytic malaria vaccines.
引用
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页数:15
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