OBJECTIVE: The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes. METHODS: Well-characterized CSP-specific neutralizing B cell epitopes and a 'universal' T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. RESULTS: The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. CONCLUSION: These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
OBJECTIVE: The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes. METHODS: Well-characterized CSP-specific neutralizing B cell epitopes and a 'universal' T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. RESULTS: The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. CONCLUSION: These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.
Authors: Lawrence T Wang; Lais S Pereira; Yevel Flores-Garcia; James O'Connor; Barbara J Flynn; Arne Schön; Nicholas K Hurlburt; Marlon Dillon; Annie S P Yang; Amanda Fabra-García; Azza H Idris; Bryan T Mayer; Monica W Gerber; Raphael Gottardo; Rosemarie D Mason; Nicole Cavett; Reid B Ballard; Neville K Kisalu; Alvaro Molina-Cruz; Jorgen Nelson; Rachel Vistein; Carolina Barillas-Mury; Rogerio Amino; David Baker; Neil P King; Robert W Sauerwein; Marie Pancera; Ian A Cockburn; Fidel Zavala; Joseph R Francica; Robert A Seder Journal: Immunity Date: 2020-09-17 Impact factor: 31.745
Authors: Milena Lange; Melanie Fiedler; Dorothea Bankwitz; William Osburn; Sergei Viazov; Olena Brovko; Abdel-Rahman Zekri; Yury Khudyakov; Michael Nassal; Paul Pumpens; Thomas Pietschmann; Jörg Timm; Michael Roggendorf; Andreas Walker Journal: PLoS One Date: 2014-07-11 Impact factor: 3.240
Authors: Hayley K Charlton Hume; João Vidigal; Manuel J T Carrondo; Anton P J Middelberg; António Roldão; Linda H L Lua Journal: Biotechnol Bioeng Date: 2018-12-31 Impact factor: 4.530