Oral vaccine sought for hepatitis B.

Oral vaccine sought for hepatitis B 

Each year in the United States, approximately300,000 people become infected with the hepatitis B virus--a major cause of acute and chronic hepatitis, cirrhosis of the liver and liver cancer. In the Third World, hepatitis B is even more prevalent, despite the availability of effective hepatitis vaccinations since 1982. Why haven't more people opted for immunization?

Widespread U.S. immunization hasbeen hampered by the high cost of the vaccine (about $115 for the required three-shot regimen) and an apparent unwillingness, even among high-risk individuals such as health care professionals and drug abusers, to undergo the injection series. Internationally, these problems are exacerbated by the shortage of sterile syringes and the need to keep the vaccine refrigerated.

Now, however, researchers report significantprogress toward developing an oral vaccine against hepatitis B--one that would require no special handling or paraphernalia and may be cheaper to produce.

Paul P. Hung and his colleagues atWyeth Laboratories in Philadelphia published the results of their work in the July PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol.84, No.13). The research team started with a live adenovirus vaccine, which in tablet form has proved effective in inducing immunity against adenovirus respiratory disease in humans. They then spliced into the adenovirus genome the coding sequence for hepatitis B surface antigen--a molecular conformation that, when recognized by the body's immune system, triggers the production of antibodies against hepatitis B. In the experiments, hamsters were inoculated through their noses with the hepatitis-B-spliced viruses, which subsequently replicated in the animals' lungs. Within 33 days, all of the hamsters had produced antibodies to both adenovirus and hepatitis B.

"Our results demonstrate the potentialutility of recombinant adenoviruses as live oral vaccines,' the authors conclude. And although they are unwilling to predict when the experiments may progress to human clinical trials, they say that "On the whole, these data indicate a good prospect for developing recombinant adenovirus vaccines that will effectively immunize humans against [hepatitis B].'

"It's certainly an unusual approach,'says Stephen C. Hadler, chief of epidemiologic activities at the Centers for Disease Control's hepatitis branch in Atlanta. Because hepatitis is not normally contracted by oral or nasal routes, he told SCIENCE NEWS, "one would anticipate major difficulties' in inducing high levels of hepatitis antibodies in the blood following oral inoculation. If effective, however, "an affordable oral hepatitis vaccine would have major potential advantages,' he says, "especially in the Third World, where it is most needed.' In comparison to intramuscular injections, oral vaccinations are much more likely to gain wide acceptance, and they cut out the potential for inadvertently transmitting other diseases with syringes, Hadler says. "The market would be huge.'

Exactly how much such a vaccinewould cost is still a matter of conjecture, however. A spokesperson for Wyeth says the oral vaccine would "probably be cheaper' than the current vaccinations, but one hepatitis specialist at Merck Sharp & Dohme--makers of the only hepatitis B vaccines currently sold in the United States--says he knows of no data to support that claim.

Meanwhile, other fruits may emergefrom Hung's research. For example, the team may have helped settle a long-standing question about the function of a particular gene sequence in the adenovirus genome. That sequence, known as the E3 region, indirectly blocks the expression of immune-cell-attracting antigens on adenovirus-infected cell surfaces, leading scientists to hypothesize that the E3 region is part of the mechanism by which an adenovirus avoids detection by the body's immune system. In accordance with this view, Hung found that adenoviruses whose E3 regions were excised in order to make room for the hepatitis B splice did not survive as long as did adenoviruses whose hepatitis splices were placed elsewhere, leaving the E3 region intact.