Vaccine manufacturers will initiate small-scale clinical studies to evaluate the safety and immunogenicity of their respective candidate H1N1 vaccines prior to initiating commercial production. CDC released the reassortant virus stock to the manufacturers back on May 27th 2009, so the H1N1 vaccine clinical studies should be starting in July.
H1N1 vaccine recipients will be immunologically naive with respect to the H1N1 virus. This is different to the situation encountered with seasonal flu vaccines, when vaccinees are usually primed by natural exposure to flu virus or by a history of flu vaccination, and only require a single dose of vaccine to achieve seroprotection. In addition, little is known about the immunogenicity of the H1N1 vaccine, so the H1N1 vaccine trials will differ from those routinely performed for seasonal vaccines.
Clinical studies for regulatory approval of seasonal vaccines evaluate a single 15 microgram dose of each of the three seasonal strains. Reviewing published clinical studies on H5N1 vaccines such as Focetria and Pandemrix, the H1N1 vaccine studies will probably evaluate a two-dose schedule (0 and 21 days) and several strengths of vaccine (probably 7.5, 15, and 30 micrograms). When the manufacturer has access to an adjuvant, there likely will be an arm of the trial that evaluates the adjuvant for dose-sparing and enhanced immunogenicity effects.
CSL of Australia have now announced that they are ready to commence a clinical trial of their H1N1 vaccine candidate, with vaccinations beginning mid-July in healthy adults between 18 and 64 years of age. They have confirmed they will evaluate a two-dose schedule of 0 and 21 days, and compare a standard dose of the vaccine with increased dosages. The standard dose would be 15 micrograms, suggesting CSL does not expect a 7.5 microgram dose of their vaccine to be sufficiently immunogenic. If this is so, and applies to other manufacturers vaccines, this will have significant impact on the the number of H1N1 vaccine doses that can be produced with the current manufacturing capacity
It should take about 6 weeks to complete and analyze the initial immunogenicity portion of the CSL clinical study, so information on proposed dose and regimen for the CSL H1N1 vaccines should be available by the end of August. Novartis have also confirmed they are initiating their clinical studies in July, so there should be some comparative data available that will begin to clarify the picture with respect to vaccine availability and capacity.
