Brussels, 19 Dec 2005
The French pharmaceutical company Sanofi-Pasteur has announced that preliminary results of clinical trials of an candidate H5N1 pre-pandemic influenza vaccine demonstrated a good response in a significant number of volunteers with smaller doses of antigen.
According to the company, the vaccine is safe, demonstrates immunogenicity and provides directions for future development.
The H5N1 bird flu strain has killed or led to the slaughter of millions of animals in parts of Asia. Since 2003, a total of 71 deaths out of 131 human cases have been reported to the WHO, leading to fears of an influenza pandemic.
A previous Sanofi-Pasteur developed flu vaccine based on H5N1, without an additional adjuvant, had shown a strong enough immune response to ward off the virus, but the doses that were most effective contained 90 micrograms of H5N1 antigen in each of two shots (180 micrograms in total). This is 12 times as much antigen as most other seasonal flu vaccines, typically containing 15 micrograms of antigen, and therefore posed a real challenge in terms of how to meet global demand in case of a pandemic.
Two possible solutions were foreseen for tackling the shortage of vaccines: one would be to increase the production capacity of existing vaccine factories, but that takes time. An alternative solution would be to improve the efficiency of vaccines, so that smaller doses of antigen are needed to protect humans against flu.
An adjuvant is a substance that is added to a vaccine to boost the body's immune response to the vaccine's antigen. Because of the ability of adjuvants to improve the body's immune response to lower doses of antigen, they allow producers to stretch the available supply of antigen.
Most current influenza virus vaccines do not contain an adjuvant, and the Sanofi-Pasteur trials were the first to compare H5N1 pre-pandemic influenza vaccines with and without adjuvants.
They tested the H5N1 vaccine being prepared for the French government on 300 volunteers, using three different doses: 7.5, 15, and 30 micrograms. The volunteers were divided into six groups, and each group received two doses of vaccine with or without alum, an adjuvant used in many vaccines. The two 30-microgram doses of vaccine containing alum induced an immune response in line with what the European Agency for Evaluation of Medicinal Products (EMEA) requires for licensure of seasonal influenza vaccines. Whilst this is an improvement on the 180 micrograms required in previous trials, it is still four times the typical 15 microgram dosage for seasonal vaccines.
A spokesperson for the World Health Organization, Dick Thompson, welcomed the results: 'This is progress and an important step in pandemic vaccine development.'
The company also noted that immune responses were detected in a number of volunteers receiving lower doses. Subsequent trials will explore different dosages, which may be helpful in answering questions about dose-sparing strategies.
The data will be submitted as part of the company's core 'mock up' vaccine dossier to the EMEA. This process is expected to reduce the time necessary for approval of a pandemic vaccine in Europe once a strain is identified and a pandemic is declared.
Sanofi-Pasteur is also participating in the EU funded FLUPAN project. This collaborative research project, funded through the 'quality of life and management of living resources' priority of the Fifth Framework Programme (FP5), aims at improve the level of pandemic preparedness in the EU. FLUPAN developed a vaccine for the H7N1 strain of avian influenza hat will be tested in clinical trials in spring 2006.