The clinical trial of 96 adults was conducted at the NIAID-supported Viral Respiratory Pathogens Research Unit at Baylor College of Medicine, Houston, and was led by Robert L. Atmar, M.D. The results are now online in Clinical Infectious Diseases.
"The results of this clinical trial add to the growing body of information demonstrating the potential value of adjuvanted avian influenza vaccines," says NIAID Director Anthony S. Fauci, M.D. An adjuvant is a substance that is added to a vaccine to boost the body's immune response to the vaccine's antigen. "In the event of an influenza pandemic, adjuvanted vaccines could provide a way to extend a limited vaccine supply to more people," he adds.
In 1999, two children in Hong Kong became infected with H9N2, a strain of avian influenza that had not previously been detected in humans. Humans have little or no natural immunity to a virus--such as H9N2 or the more deadly H5N1 avian influenza--that historically has circulated only in birds. If H9N2 or H5N1 were to acquire the ability to spread easily from person to person, an influenza pandemic could result, health experts say.
In 2004, NIAID directed Novartis Vaccines and Diagnostics (formerly Chiron Corporation) to produce 40,000 doses of an experimental H9N2 vaccine at its vaccine manufacturing facility in Siena, Italy. Some of the vaccines were formulated with Novartis's MF59 adjuvant. (See http://www3.niaid.nih.gov/news/newsreleases/2004/h9n2.htm.)
Dr. Atmar and his colleagues tested the vaccines in volunteers aged 18 to 34 in this Phase I clinical trial. Phase I vaccine trials assess candidate vaccines' safety and ability to stimulate an immune system response, and are not designed to determine whether the vaccine would prevent infection by naturally occurring virus. The researchers vaccinated 48 volunteers with non-adjuvanted H9N2 vaccine (made from inactivated virus) at one of four dosages--3.75, 7.5, 15 or 30 micrograms. An additional 48 volunteers received MF59-adjuvanted vaccine at one of the same four dosages. Volunteers were vaccinated twice, with inoculations spaced 28 days apart.
An avian flu vaccine, like the seasonal flu vaccine, should stimulate antibodies, which help ward off infection if the vaccinated person later encounters the flu virus. In general, the higher the level of antibodies made in response to a vaccine, the more protective the vaccine is, Dr. Atmar notes.
"In our trial, a single inoculation of adjuvant-containing H9N2 vaccine, even at the lowest dosage, generated a good antibody response," says Dr. Atmar. By comparison, the seasonal flu vaccine contains 15 micrograms each of three different circulating flu strains--much higher than the 3.75 micrograms of H9N2 flu virus contained in the lowest dose vaccine tested in this trial. Furthermore, he adds, a single dose of the adjuvanted H9N2 vaccine was as good as two doses of the vaccine without adjuvant.
Currently, MF59 is licensed for use as a vaccine adjuvant in Europe but not in the United States. The results of this trial, says Dr. Atmar, suggest that MF59 is deserving of further study.