Back HCV Prevention HCV Vaccines Experimental HCV Vaccine Induces Broadly Neutralizing Antibodies in Mice and Monkeys

Experimental HCV Vaccine Induces Broadly Neutralizing Antibodies in Mice and Monkeys

alt

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.

Results

  • 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.

8/5/11

 

References

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.

Other Source

AAAS. Science Translational Medicine Press Package for 3 August 2011.