Monoclonal Antibody May Help Prevent and Clear Hepatitis C Virus

A human monoclonal antibody dubbed HCV1 was able to prevent exposed chimpanzees from becoming infected with hepatitis C virus, and chimps with acute and chronic infection experienced reductions in HCV viral load, according to a study published in the August 30, 2012, issue of the open-access journal PLoS Pathogens.

While hepatitis C treatment has improved with the introduction of direct-acting antiviral agents, there is still no effective HCV vaccine or other proven biomedical prevention methods, nor is it known how to stop acute infection from becoming chronic.

Trevor Morin from MassBiologics at the University of Massachusetts and colleagues tested whether the HCV1 monoclonal antibody could protect chimps from HCV infection. HCV1 binds to a conserved section of HCV's E2 envelope glycoprotein and neutralizes a broad range of HCV genotypes; previous studies showed that the antibody blocks HCV from entering liver cells in laboratory cultures.

Chimpanzees -- the only species besides humans susceptible to HCV infection --  received a single 50 or 250 mg/kg dose of HCV1, delivered 30 minutes prior to challenge with an infusion of genotype 1a HCV.

The study was designed to see if the monoclonal antibody could protect the liver from the type of exposure that would occur in the setting of liver transplantation. In nearly all people with hepatitis C who receive a transplant, the liver graft is eventually infected by HCV. "Infection of the new donor liver by residual virus in the patient is one of the major obstacles preventing a full recovery," saidstudy co-author Robert Lanford in a press release issued by the Texas Biomedical Research Institute.

The researchers found that the 250 mg/kg dose of HCV1 provided complete protection against infection, but the lower dose was not effective. In addition, an acutely infected chimp given 250 mg/kg of HCV1 at 42 days after viral exposure experienced a rapid reduction in HCV viral load to below the limit of detection. Viral rebound occurred 14 days later with virus showing an E2 mutation that conferred resistance to HCV1 neutralization.

The study also found that 3 chimps with chronic HCV infection treated with a single 40 mg/kg dose of HCV1 experienced viral load reduction. One animal had HCV RNA below the limit of detection for 21 days, and the rebounding virus had an HCV1 resistance mutation; 2 other chimps had viral load reductions of 0.5 to 1.0 log, without evidence of viral resistance to HCV1.

"These data suggest that human monoclonal antibody HCV1 may be an effective therapeutic for the prevention of graft infection in HCV-infected patients undergoing liver transplantation," the researchers suggested.

"One can envision improving on these results with a cocktail of antibodies or by using this antibody with some of the newer antivirals currently in clinical trials," added Lanford.

9/5/12

Reference

TJ Morin, TJ Broering, BA Leav, et al. Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees. PLoS Pathogens 8(8):e1002895. August 30, 2012.

Other Source

Texas Biomedical Research Institute. Antibody Prevents Hepatitis C Infection in Animal Model. Press release. August 30, 2012.