Hesitations over Hungary’s H5N1 vaccine

Scientists say it is unlikely that the developed world will soon benefit from Hungary’s recent decision to commercialize the first H5N1 vaccine for humans, which has already captured the interest of some countries. While the World Health Organization calls the early data “encouraging,” researchers describe them as too limited — and preliminary — to determine whether or not the vaccine works. “It’s very hard to assess when you don’t have more information,” William Schaffner from the Vanderbilt University School of Medicine, in Nashville, TN, told The Scientist. “A lot is missing from the data — they still seem to be at very early stages.”

The vaccine was initially developed in September 2005 by Hungary’s National Center of Epidemiology, now collaborating with local company Omninvest to produce 500,000 doses a week. According to Klaus Stohr, who coordinates the WHO global influenza program, Hungary presented “encouraging” preliminary findings during a WHO meeting last November. During a study, Hungarian scientists combined 30 micrograms of the whole H5N1 virus with the conventional adjuvant Alum. In the trial, 146 volunteers received the H5N1 virus inoculation, and blood samples were collected one, three and six months after vaccination.

In the publicly released data, the number of seroconversions after 21 days reached 63%, exceeding the target of 40%. The mean geometric increase of hemagglutination inhibition (HI) titers also suggested the vaccine was offering some protection. However, the proportion of subjects achieving an HI titer was only 63%, less than the expected 70%. The researchers have also not yet released 90-day and 180-day serological analyses, which measure the vaccine’s long-lasting effects. Omninvest spokesperson Zsolt Nemeth noted that the vaccine should work if at least one of the above three values — number of seroconversions, mean geometric increase of HI titers, and the proportion of subjects achieving an HI titer — meets expectations.

However, Schaffner noted that meeting one expectation is not enough. “In the US, we would not just be satisfied with achieving just one of these specifications, but all of them.” He added that there are many missing details, such as the age limit of study participants and their immunocompetence. Faced with such limited information, representatives at institutions such as the Center for Disease Control and the National Institute of Health told The Scientist that staff scientists did not feel comfortable commenting on the effectiveness of the vaccine.

Ian Gust, from the University of Melbourne in Australia, told The Scientist that the Hungarians employed a method that most of the developed world has not used in at least forty years. “It is a relatively crude process that was associated with a lot of reactions in people who received the vaccine in the past,” he said. “I don’t think developed countries would revert to this.” Most of the developed world’s manufacturers are working on H5N1 vaccines, containing split and whole viruses, but are “using more sophisticated production processes.”

Gust added that many aspects of the Hungarian vaccine remain a mystery. “The data currently available is too limited and, as far as I know, there hasn’t been any independent tests made by an outside laboratory.” Schaffner suggested it is unlikely that the US would be interested in the vaccine based on the current public information, despite the fact that it has captured the interest of some countries, including Romania. He added that the vaccine may be more attractive to Eastern European countries, some of which can’t produce a vaccine themselves. “It might be attractive for them to go for a manufacturer that’s local, probably less expensive, and quick,” he said.

The Scientist
April 11, 2006

Original web page at The Scientist