Adenovirus based HPV L2 vaccine induces broad cross-reactive humoral immune responses

Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Marija Vujadinovic, Selina Khan, Koen Oosterhuis, Taco G. Uil, Kerstin Wunderlich, Sarra Damman, Satish Boedhoe, Annemiek Verwilligen, Jonathan Knibbe, Jan Serroyen, Hanneke Schuitemaker, Roland Zahn, Gert Scheper, Jerome Custers, Jort Vellinga
Oncogenic high-risk human papillomavirus (HPV) infections cause a substantial number of genital and non-genital cancers worldwide. Approximately 70% of all cervical cancers are caused by the high-risk HPV16 and 18 types. The remaining 30% can be attributed to twelve other high-risk HPV-types. Highly efficacious 2-valent, 4-valent and 9-valent L1 protein based prophylactic HPV vaccines are available however with limited cross-protection. To further increase the coverage, development of a multivalent cross-protective HPV vaccine is currently focused on the conserved N-terminus of HPV’s L2 protein. We have developed a vaccine candidate based on the rare human adenovirus type 35 (HAdV35) vector that displays a concatemer of L2 protein epitopes from four different HPV-types via protein IX (pIX). A mix of two heterologous HAdV35 pIX-L2 display vectors present highly conserved linear epitopes of nine HPV-types. Each HAdV35 pIX-L2 display vector exhibits a good manufacturability profile. HAdV35 pIX-L2 display vaccine vectors were immunogenic and induced neutralizing antibodies against HPV-types included in the vaccine and cross-neutralizing antibodies against distant a HPV-type not included in the vaccine in mice. The HAdV35 pIX-L2 display vectors offer an opportunity for a multivalent HAdV-based prophylactic HPV vaccine.