December 17, 2005
Adjuvanted H5N1 Vaccine Trial in France shows Antigen-Sparing Effect
On 15 December preliminary results were posted online (http://en.sanofi-aventis.com/press/p_press_2005.asp) from an H5N1 vaccine trial in France by Sanofi Pasteur with and without a vaccine adjuvant to boost the immune response. These initial results, not yet published in a medical journal, are reportedly encouraging according to the announcement by the company (Sanofi Pasteur).
Specifically, Sanofi Pasteur reported what they consider sufficient immune responses for flu vaccine licensure by regulatory agencies after two shots of a vaccine containing only 30 micrograms (ug) of the H5N1 vaccine antigen combined with an (unnamed) adjuvant.
This 30ug of H5N1 vaccine antigen is a 3-fold reduction from the 90 ug of H5N1 vaccine antigen required in the initial H5N1 vaccine trial in the USA to achieve a similar immune response using a vaccine that did not contain an adjuvant. Hence, use of the adjuvant in this clinical trial of 300 health volunteers at three places in France: Necker and Cochin Hospitals in Paris, and Garches Hospital, would represent a 3-fold “antigen-sparing effect” in that only 30ug of H5N1 vaccine antigen instead of 90ug was needed to achieve a desired level of immune response.
No data was provided to compare the duration of the immune response against H5N1 in either of these two vaccine trials. Duration as well as peak level of an immune response is clinically important in terms of how ell and for how long an immune response will protect against infection, or symptomatic disease, due to influenza.
Additional H5N1 vaccine study results are awaited form the ongoing clinical trial in Australia, the recently clinical trial in Hungary, and anticipated H5N1 vaccine trials in 2006 in Asia, including but not limited to Vietnam, Japan, and Thailand. Comparing one or more adjuvants, and use of intradermal route of immunization to maximize the antigen-sparing effect is critical toward being able to vaccinate as many persons as possible with the future pandemic flu vaccine that will only be possible once a pandemic influenza virus has “emerged” either related to H5N1 or to another influenza virus.
The rational assumption is that the lessons-learned now with H5N1 vaccines will apply to the future pandemic influenza vaccines after a pandemic flu virus appears once again in the world as it did in 1918, 1957, and 1968. Once again, with many emerging or reemerging diseases, the “past is prologue” to the future. If we fail to prepare sufficiently, then the damage will be obvious on a global scale for years to come.
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases
ER One Institutes, Washington Hospital Center
Co-Director, M.S. Program in Biohazardous Threat Agents and Emerging Diseases
Georgetown University School of Medicine, Washington, DC
Website: www.BePast.org; E-mail: Daniel.R.Lucey@Medstar.net