Combination of vaccine and antiviral fractures immune tolerance

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   Source:  Virus Weekly, June 11, 2002 p2.
                                                                              
    Title:  Combination of vaccine and antiviral fractures immune tolerance in
            virus model.(Brief Article)
                                                                              
Subjects:  Hepatitis B - Infective ability
            Marmots - Diseases
            Cellular immunity - Effect of drugs on
            Vaccines industry - Research
Locations:  United States
SIC code:  8730;  2836
                                                                              
Electronic Collection:  A86825149
                   RN:  A86825149
                                                                              

Full Text COPYRIGHT 2002 NewsRX

2002 JUN 11 - (NewsRx.com & NewsRx.net) -- by Sonia Nichols, senior medical writer - Woodchuck hepatitis virus (WHV) infects woodchucks in a manner similar to the way hepatitis B virus (HBV) infects humans. Using woodchucks infected with WHV, U.S. investigators have shown how combining an antiviral with surface antigen vaccination can break humoral and cell-mediated immune tolerance in infected animals.

For the study, research collaborators at Cornell University in Ithaca, New
York, and at the Georgetown University Medical Center facility in Rockville,
Maryland, first treated several WHV-infected woodchucks with
1-(2-fluoro-5-methyl-Beta-L-arabinofuranosyl)-uracil (L-FMAU), an antiviral
agent, for 8 months. Several other infected animals received placebo.

The investigators then inoculated several animals from both groups with four injections of WHV vaccine containing surface antigen during the following 4 months.

"Vaccination alone elicited a low-level antibody response to surface antigen
in most carriers but did not affect serum WHV DNA and surface antigen,"
reported Stephan Menne of the Department of Clinical Sciences at Cornell.
Similar antibody response was observed in animals pretreated with the
antiviral, the team noted.

Both sets of animals exhibited cell-mediated immunity to surface antigen
following the vaccinations, but the effect of vaccination was more extensive
in animals that had received L-FMAU, as investigators identified response to
viral antigens other than just surface antigen (Immunization with surface
antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-Beta-L-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection, Journal of Virology, June 2002;76(11):5305-5314).

In animals that received L-FAMU only, both cell-mediated immunity and humoral immunity could be detected in 50% of the animals after that therapy was ended, study data indicated.

"Surface antigen vaccine alone or in combination with drug broke humoral and cell-mediated immune tolerance in chronic WHV infection, but the combination with drug was more effective," commented Menne and coauthors. "This suggested that a high viral and antigen load in carriers is important in maintaining immunologic tolerance during chronicity," they added.

Menne and colleagues suggested that combining analogous therapies for humans could be a useful way to attack chronic hepatitis B infections.

The corresponding author for this study is Stephan Menne, Gastrointestinal
Unit, Dept. of Clinical Sciences, College of Veterinary Medicine, Room C-2005
VMC, Cornell University, Ithaca, NY 14853, USA. E-mail: [email protected].

Key points reported in this study include:

* A combination of surface antigen vaccine and the antiviral L-FMAU induced
enhanced antibody response in animals infected woodchuck hepatitis virus

* The vaccine-antiviral combination was more effective for boosting
cell-mediated immunity in animals infected with woodchuck hepatitis virus

* A vaccine-antiviral combination could possibly be used to break immune
tolerance in humans infected with hepatitis B virus

This article was prepared by Virus Weekly editors from staff and other
reports.
                                                                              
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