- Category: HCV Vaccines
- Published on Friday, 05 August 2011 00:00
- Written by Liz Highleyman
French researchers have taken a further step toward the elusive goal of a vaccine for hepatitis C, using virus-like particles that stimulate a broad neutralizing antibody response effective against multiple HCV genotypes, according to a report in the August 3, 2011, issue of Science Translational Medicine.
Hepatitis C virus (HCV) mutates extensively as it replicates, leaving an infected individual with a wide array of variant strains. This diversity helps the virus evade the immune system and makes it difficult to create a broadly active vaccine that can protect against multiple variants. While effective vaccines exist for hepatitis A and B, hepatitis C more closely resembles HIV in the difficulty of the task.
Pierre Garrone from Epixis S.A. in Lyon and colleagues developed an investigational vaccine based on "pseudotyped" virus-like particles (VLPs) made with a retroviral Gagprotein.
These particles resemble viruses, but since they do not contain viral genetic material they cannot replicate and therefore are non-infectious. The vaccine was designed to elicit production of broadly neutralizing antibodies, or NAbs, that can recognize multiple viral strains.
- VLPs "pseudotyped" with the HCV envelope glycoproteins E1 or E2 stimulated production of high titers of anti-E1 or anti-E2 antibodies.
- The VLP vaccine also elicited production of neutralizing antibodies in both mice and macaque monkey.
- Neutralizing antibodies produced in response to HCV genotype 1a were also able to cross-neutralize 5 other genotypes: 1b, 2a, 2b, 4, and 5.
Thus, the study authors concluded, "the described VLP platform, which can be pseudotyped with a vast array of virus envelope glycoproteins, represents a new approach to viral vaccine development."
"These results, when considered in the context of an earlier clinical trial that used recombinant HCV E1/E2 purified protein as a subunit vaccine and additional findings from the VLP strategy, may lead to a new HCV vaccine that induces a neutralizing antibody response," wrote Ranjit Ray from Saint Louis University in an accompanying editorial perspective.Investigator affiliations: Epixis S.A., Lyon, France; Université de Lyon, Université Claude Bernard Lyon I, INSERM U758; ENS de Lyon, France; CEA, Service de Neurovirologie (DSV/DRM), CRSSA, Institut Paris-Sud sur les Cytokines, Fontenay aux Roses, France; Université Pierre et Marie Curie Paris 06, Immunology-Immunopathology-Immunotherapy (I3), Paris, France; CNRS, UMR7211, I3, Paris, France; INSERM, UMR_S959, I3, Paris, France; Unité de Génomique Virale et Vaccination, Department of Virology, Institut Pasteur, CNRS URA 3015, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy, Paris, France; Epixis S.A., Paris, France.
P Garrone, A Fluckiger, P Mangeot, et al. A prime-boost strategy using virus-like particles pseudotyped for HCV proteins triggers broadly neutralizing antibodies in macaques. Science Translational Medicine 3(94):94ra71 (abstract). August 3, 2011.
R Ray. Progress Toward Development of a Hepatitis C Vaccine with Broad Shoulders. Science Translational Medicine 3(94): 94ps33 (abstract). August 3, 2011.
AAAS. Science Translational Medicine Press Package for 3 August 2011.