Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins.
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.
a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics; National Institute of Diagnostics and Vaccine Development in Infectious Diseases; Xiamen University ; Xiamen , Fujian , PR China.
Xiao
X
Zhang
Lu
L
Xin
Shaowei
S
Li
Mujin
M
Fang
Jun
J
Zhang
Ningshao
N
Xia
Qinjian
Q
Zhao
D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D055808:Drug Discovery / Q000379:methods; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053918:Papillomavirus Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013678:Technology, Pharmaceutical / Q000379:methods; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D036022:Capsid Proteins; D000939:Epitopes; D053918:Papillomavirus Vaccines; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014761:Viral Hepatitis Vaccines
capsid protein; conformation-dependent epitope; human vaccine; immunodominant epitopes; neutralizing antibodies; virus-like particle