Therapeutic hepatitis B vaccine may lead to functional cure

Liz Highleyman
Published:
13 November 2019
Osamu Yoshida Ehime of University School of Medicine in Japan presenting results of a study of a dual-antigen therapeutic vaccine at the 2019 Liver Meeting, Boston. Photo by Liz Highleyman.

An experimental therapeutic vaccine called NASVAC, which targets two different hepatitis B virus (HBV) antigens, led to a reduction in hepatitis B surface antigen (HBsAg) levels, according to study presented this week at the AASLD Liver Meeting in Boston. What's more, a small number of study participants experienced HBsAg loss, considered a functional cure.

Currently approved HBV preventive vaccines contain HBsAg. Although generally effective, a small proportion of people do not achieve protective antibody levels. Targeting additional HBV antigens could lead to stronger immune responses that are beneficial for both prevention and treatment. An experimental prevention vaccine called Sci-Vac-B, which contains three HBV antigen, was recently shown to offer greater protection, especially for older adults and people with weak immune systems.

At the Liver Meeting, Osamu Yoshida of Ehime University School of Medicine in Japan presented results from a study of a dual-antigen therapeutic vaccine for the treatment of people with hepatitis B who either were either taking antiviral therapy or had inactive HBV infection.

Nucleoside/nucleotide antivirals such as tenofovir disoproxil fumarate (Viread), tenofovir alafenamide (Vemlidy) or entecavir (Baraclude) can suppress HBV replication indefinitely during treatment, but they seldom lead to a cure. Across studies, around 10% of people treated with pegylated interferon, about 5% of hepatitis B 'e' antigen (HBeAg) positive people treated with antivirals and as few as 0% of HBeAg negative people treated with antivirals achieve HBsAg loss.

Antiviral treatment is generally not recommended for people with inactive infection who have low HBV viral load, low ALT liver enzyme levels and no evidence of liver cirrhosis. However, such individuals may still transmit the virus and are at elevated risk for liver cancer.

NASVAC, initially developed by the Center for Genetic Engineering and Biotechnology in Cuba, contains both HBsAg and hepatitis B core antigen (HBcAg). The HBsAg component triggers production of anti-HBs antibodies, while the HBcAg component promotes T-cell activity that inhibits HBV replication. The nasally administered vaccine has been evaluated for both prevention and treatment.

The current study included 29 participants on antiviral therapy and 42 untreated people with inactive hepatitis B. In the treated group, more than 70% were men, the median age was 54 years and about three-quarters were HBeAg negative. Nearly half were taking entecavir and about 40% were taking one of the two versions of tenofovir; all had undetectable HBV DNA. In the untreated group, over half were women, the median age was 53 and 95% were HBeAg negative. Both groups had ALT and AST levels within the normal range.

Participants in this open-label study received NASVAC every two weeks, for a total of ten doses. They were followed for up to six months after the last dose.

NASVAC administration had little effect on viral load. People on antiviral therapy maintained undetectable HBV DNA levels, while untreated participants saw a non-significant decrease of 10.5%.

However, the vaccine did reduce HBsAg levels in three-quarters of participants in both groups. HBsAg declined by an average of 16.7% from baseline in the antiviral group and by 18.3% in the untreated group; both declines were statistically significant.

Two people in each group experienced HBsAg loss – far higher than the rates typically seen in HBeAg-negative people treated with antiviral therapy.

Looking at immune responses, 37.9% of participants in the antiviral therapy group and 58.5% in the untreated group produced anti-HBs antibodies after receiving the vaccine. A few also developed anti-HBe antibodies.

Treatment was generally safe and well tolerated, with no severe adverse events. ALT levels remained stable in the antiviral group. In the untreated group, three people experienced steep but transient ALT increases. In one individual, anti-HBs antibodies rose at the time of the elevation and she experienced HBeAg loss after the ALT flare.

Based on these findings, the researchers concluded, "NASVAC could be a novel immune therapy for achieving functional cure in HBV-infected patients."

Reference

Yoshia O et al. Induction of anti-HBs and reduction of HBsAg by nasal administration of a therapeutic vaccine containing HBsAg and HBcAg (NASVAC) in patients with chronic HBV infection. AASLD Liver Meeting, Boston, abstract 0088, 2019. Hepatology 70:60A, 2019.

https://plan.core-apps.com/tristar_aasld19/abstract/0b8716de6c519b8c26b6b46a1152262c