Development of a recombinant vaccine against human onchocerciasis

被引:9
作者
Abraham, David [1 ]
Graham-Brown, John [2 ]
Carter, Darrick [3 ]
Gray, Sean A. [3 ]
Hess, Jessica A. [1 ]
Makepeace, Benjamin L. [2 ]
Lustigman, Sara [4 ]
机构
[1] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA
[2] Univ Liverpool, Inst Infect Vet & Ecol Sci, Liverpool, Merseyside, England
[3] PAI Life Sci Inc, Seattle, WA USA
[4] New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Mol Parasitol, New York, NY 10021 USA
关键词
Onchocerca volvulus; Onchocerca ochengi; fusion protein; recombinant vaccine antigens; onchocerciasis; TOVA; vaccine against onchocerciasis; 3RD STAGE LARVAE; PROTECTIVE IMMUNITY; ANTIBODY-RESPONSES; GENETIC-POLYMORPHISM; MULTIPLE TREATMENTS; VOLVULUS INFECTION; ACQUIRED-IMMUNITY; FILARIAL NEMATODE; ANTIGEN VACCINE; BOVINE MODEL;
D O I
10.1080/14760584.2021.1977125
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction Human onchocerciasis caused by the filarial nematode parasite Onchocerca volvulus remains a major cause of debilitating disease infecting millions primarily in Sub-Saharan Africa. The development of a prophylactic vaccine, along with mass drug administration, would facilitate meeting the goal of onchocerciasis elimination by 2030. Areas covered Models used to study immunity to Onchocerca include natural infection of cattle with Onchocerca ochengi and O. volvulus infective third-stage larvae implanted within diffusion chambers in mice. A vaccine, comprised of two adjuvanted recombinant antigens, induced protective immunity in genetically diverse mice suggesting that it will function similarly in diverse human populations. These antigens were recognized by immune humans and also induced protective immunity against Brugia malayi. We describe the development of a fusion protein composed of the two vaccine antigens with the plan to test the vaccine in cows and non-human primates as a prelude to the initiation of phase 1 clinical trials. Expert opinion The adjuvanted O. volvulus vaccine composed of two antigens Ov-103 and Ov-RAL-2 was shown to be consistently effective at inducing protective immunity using multiple immune mechanisms. The vaccine is ready for further evaluation in other animal models before moving to clinical trials in humans.
引用
收藏
页码:1459 / 1470
页数:12
相关论文
共 126 条
[1]   Immunoglobulin E and eosinophil-dependent protective immunity to larval Onchocerca volvulus in mice immunized with irradiated larvae [J].
Abraham, D ;
Leon, O ;
Schnyder-Candrian, S ;
Wang, CC ;
Galioto, AM ;
Kerepesi, LA ;
Lee, JJ ;
Lustigman, S .
INFECTION AND IMMUNITY, 2004, 72 (02) :810-817
[2]   Immunity to Onchocerca spp. in animal hosts [J].
Abraham, D ;
Lucius, R ;
Trees, AJ .
TRENDS IN PARASITOLOGY, 2002, 18 (04) :164-171
[3]   SURVIVAL AND DEVELOPMENT OF LARVAL ONCHOCERCA-VOLVULUS IN-DIFFUSION CHAMBERS IMPLANTED IN PRIMATE AND RODENT HOSTS [J].
ABRAHAM, D ;
LANGE, AM ;
YUTANAWIBOONCHAI, W ;
TRPIS, M ;
DICKERSON, JW ;
SWENSON, B ;
EBERHARD, ML .
JOURNAL OF PARASITOLOGY, 1993, 79 (04) :571-582
[4]   Development of a recombinant antigen vaccine against infection with the filarial worm Onchocerca volvulus [J].
Abraham, D ;
Leon, O ;
Leon, S ;
Lustigman, S .
INFECTION AND IMMUNITY, 2001, 69 (01) :262-270
[5]   Successful vaccination against Onchocerca ochengi infestation in cattle using live Onchocerca volvulus infective larvae [J].
Achukwi, M. D. ;
Harnett, W. ;
Enyong, P. ;
Renz, A. .
PARASITE IMMUNOLOGY, 2007, 29 (03) :113-116
[6]   Onchocerca ochengi acquisition in zebu Gudali cattle exposed to natural transmission:: parasite population dynamics and IgG antibody subclass responses to Ov10/Ov11 recombinant antigens [J].
Achukwi, MD ;
Harnett, W ;
Bradley, J ;
Renz, A .
VETERINARY PARASITOLOGY, 2004, 122 (01) :35-49
[7]  
[Anonymous], 2014, WORLD HLTH ORG
[8]   Genomic organization and effects of ivermectin selection on Onchocerca volvulus P-glycoprotein [J].
Ardelli, BF ;
Guerriero, SB ;
Prichard, RK .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2005, 143 (01) :58-66
[9]   Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection [J].
Arumugam, Sridhar ;
Wei, Junfei ;
Liu, Zhuyun ;
Abraham, David ;
Bell, Aaron ;
Bottazzi, Maria Elena ;
Hotez, Peter J. ;
Zhan, Bin ;
Lustigman, Sara ;
Klei, Thomas R. .
PLOS NEGLECTED TROPICAL DISEASES, 2016, 10 (04)
[10]   An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana [J].
Awadzi, K ;
Boakye, DA ;
Edwards, G ;
Opoku, NO ;
Attah, SK ;
Osei-Atweneboana, MY ;
Lazdins-Helds, JK ;
Ardrey, AE ;
Addy, ET ;
Quartey, BT ;
Ahmed, K ;
Boatin, BA ;
Soumbey-Alley, EW .
ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY, 2004, 98 (03) :231-249