The problem with vaccines that have been developed so far is that they need two large doses per person to be effective, too much to be widely used in a pandemic. But vaccination with a non-pandemic strain virus may be enough to dramatically improve immune responses when people are later immunized a single dose.
This priming might be a way to ensure that there would be at least enough vaccine to protect key groups -- health care workers or the military, for instance -- in the event of a pandemic, said Nega Ali Goji, M.D., of the University of Rochester (N.Y.) Medical Center.
Current work on avian flu vaccines shows that they are immunogenic after two doses of 90 mcg each, Dr. Goji told a late-breaking symposium at Infectious Diseases Society of America meeting here.
But the world's vaccine manufacturing capacity is limited, he said, so that strategies to work with lower or fewer doses will be essential in the event of an avian flu pandemic, which some experts fear is only a matter of time.
Dr. Goji and colleagues took advantage of an earlier randomized placebo-controlled study, conducted in 1998 at Rochester, that evaluated the effects of a vaccine against a clade 3 H5N1 vaccine isolated in Hong Kong.
They enrolled 37 members of the group that received the 1998 vaccine and 103 volunteers who had never been given an H5 vaccine, Dr. Goji said.
All volunteers were given 90 mcg of the clade 1 vaccine that was tested and found immunogenic earlier this year. The naÃ¯ve volunteers were then given a second dose 28 days later, and immune responses were compared then and again at day 56.
The researchers found:
- When the first dose was given, immune responses were comparable in terms of geometric mean titers of both hemagglutination inhibition antibody (HAI) and serum neutralizing antibody.
- At day 28, when they got their second dose, the naÃ¯ve volunteers had an HAI geometric mean titer of 13.3 and a serum neutralizing antibody titer of 16.6.
- At the same point, the primed volunteers had HAI titers of 64.0 and 187.6, respectively.
- Both measures increased at day 56 for the naÃ¯ve volunteers, but still remained lower than what was seen in the primed subjects.
Dr. Goji said the vaccine was well-tolerated in both study groups.
The finding opens the possibility that some workers might be immunized with an H5N1 variant and then boosted with a vaccine against a future pandemic strain, but Dr. Goji cautioned that the study needs to be replicated with larger numbers.
Nonetheless, the result is "very definitely a positive finding," commented Kathleen Neuzil, M.D., or the University of Washington and the chair of the association's pandemic influenza task force.
"We see that the virus is changing, and so the fact that you can prime ahead of time and there still is enough relatedness to give you a response, to me is a very positive outcome of the trial," Dr. Neuzil said.
In a statement, Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, echoed Dr. Neuzil's comments. The institute provided financial support for the Rochester trial.
"These preliminary findings need to be confirmed in larger studies, but they offer the intriguing possibility that pre-pandemic priming with existing H5N1 vaccines may boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging human influenza pandemic," Dr. Fauci said.
- Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine