Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine

被引:176
作者
Collins, Katharine A. [1 ]
Snaith, Rebecca [1 ]
Cottingham, Matthew G. [1 ]
Gilbert, Sarah C. [1 ]
Hill, Adrian V. S. [1 ]
机构
[1] Univ Oxford, Jenner Inst Labs, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England
基金
英国惠康基金;
关键词
PLASMODIUM-FALCIPARUM ANTIGENS; T-CELL IMMUNITY; CIRCUMSPOROZOITE-PROTEIN; ANTIBODY-RESPONSES; EPITOPE DENSITY; EFFICACY; SAFETY; IMMUNIZATION; COMBINATION; MECHANISMS;
D O I
10.1038/srep46621
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The leading malaria vaccine in development is the circumsporozoite protein (CSP)-based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy, thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and therefore developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a vaccine composed of a much higher proportion of CSP than in RTS,S. We demonstrate that in BALB/c mice R21 is immunogenic at very low doses and when administered with the adjuvants Abisco-100 and Matrix-M it elicits sterile protection against transgenic sporozoite challenge. Concurrent induction of potent cellular and humoral immune responses was also achieved by combining R21 with TRAP-based viral vectors and protective efficacy was significantly enhanced. In addition, in contrast to RTS,S, only a minimal antibody response to the HBsAg carrier was induced. These studies identify an anti-sporozoite vaccine component that may improve upon the current leading malaria vaccine RTS,S. R21 is now under evaluation in Phase 1/2a clinical trials.
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页数:15
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