Article
作者: King, Lloyd D W  ; Long, Carole A  ; Howarth, Mark R  ; Rees-Spear, Chloe  ; Li, Yuanyuan  ; Diouf, Ababacar  ; Suurbaar, Jonathan  ; Draper, Simon J  ; Pattinson, David J  ; Fleishman, Sarel J  ; Silk, Sarah E  ; MacGill, Randall S  ; Biswas, Sumi  ; Birkett, Ashley J  ; Davies, Hannah  ; Lias, Amelia M  ; Noe, Amy R  ; Rigby, Cassandra A  ; Skinner, Katherine  ; Zhou, Yu  ; Rodrigues, Ana  ; McHugh, Kirsty  ; Ashfield, Rebecca  ; Barrett, Jordan R  ; King, C Richter  ; Pulido, David  ; Minassian, Angela M  ; Quinkert, Doris  ; Strazza, Veronica  ; Carnrot, Cecilia  ; Miura, Kazutoyo  ; Jin, Jing  ; Campeotto, Ivan  ; Dabbs, Rebecca A  ; Williams, Barnabas G  ; Gupta, Gaurav  ; Soisson, Lorraine A  ; Ishizuka, Andrew S 
Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.