Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins

Abstract

Recombinant VLP-based vaccines have been successfully used against 3 diseases caused by viral infections: Hepatitis B, cervical cancer and hepatitis E. The VLP approach is attracting increasing attention in vaccine design and development for human and veterinary use. This review summarizes the clinically relevant epitopes on the VLP antigens in successful human vaccines. These virion-like epitopes, which can be delineated with molecular biology, cryo-electron microscopy and x-ray crystallographic methods, are the prerequisites for these efficacious vaccines to elicit functional antibodies. The critical epitopes and key factors influencing these epitopes are discussed for the HEV, HPV and HBV vaccines. A pentamer (for HPV) or a dimer (for HEV and HBV), rather than a monomer, is the basic building block harboring critical epitopes for the assembly of VLP antigen. The processing and formulation of VLP-based vaccines need to be developed to promote the formation and stabilization of these epitopes in the recombinant antigens. Delineating the critical epitopes is essential for antigen design in the early phase of vaccine development and for critical quality attribute analysis in the commercial phase of vaccine manufacturing.

Integrated molecular and bioprocess engineering for bacterially produced immunogenic modular virus‐like particle vaccine displaying 18 kDa rotavirus antigen

“…The use of synthetic biology for vaccine design is one of the strategies that have gained attention for addressing manufacturing and processing gaps of vaccine candidates. With the aid of synthetic biology and computational tools (Lua et al, ; Zhang et al, ), full length, or truncated proteins or small peptide epitopes have been molecularly inserted into viral structural proteins to generate a new class of bioengineered modular VLP vaccines (Lua et al, ; Zhang et al, ). Insertion of a RV 18 kDa VP8* antigen into the protrusion (P) domain of the norovirus capsid protein produced a highly immunogenic modular VLP subunit vaccine against RVs inside E. coli cells (Tan et al, ).…”

Protection induced by early stage vaccination with pandemic influenza virus-like particles

“…These clinical studies demonstrated the safety and efficacy of influenza VLP vaccines, and provided an important rationale for developing VLP vaccine technology. Since baculovirus expressed VLPs contain live baculovirus and baculovirus DNA, the further improvement of the VLP production processes would be highly beneficial to eliminate baculovirus particle and DNA [24,25].…”

Rotavirus virus‐like particles (RV‐VLPs) vaccines: An update

“…They consist of the host envelope protein integrated with target antigens over its outer surface that overall mimics the authentic virus particle. VLP‐based vaccines that are already in use are developed against hepatitis b virus and human papillomavirus, while others targeting chikungunya virus, human immunodeficiency virus, and influenza virus have entered the clinical evaluation phase …”