Whole-virus formulation leads to dose-sparing H5N1 vaccine
in the event of an avian influenza pandemic after a clinical trial
showed that their formulation containing the whole H5N1 virus
instead of virus particles resulted in an affective immune response
at lower doses.
The results of the trial, published in The Lancet, showed that a 10µg vaccine using whole virus was as effective as a 30µg vaccine using virus particles, without any difference in the frequency of reported side-effects.
This is important because whole-virus vaccines are known to cause more side-effects, something that was thought to offset the greater immune response they triggered.
But the scientists involved in the study, from the Beijing-based firm Sinovac Biotech and the Chinese Centre for Disease Control and Prevention, discovered that pain, swelling and fever were observed equally in the 120 healthy volunteers used in the study irrespective of whether the formulation was based on whole virus or particles, or placebo for that matter.
"During a pandemic, the demand for influenza vaccines will far outstrip the manufacturing capacity of such vaccines, a situation that has led to the World Health Organisation (WHO) encouraging investigation into dose-sparing strategies, including the use of adjuvants and whole-virion vaccine," said author Weidong Yin from Sinovac Biotech.
"Our trial suggests that an H5N1 vaccine manufactured and formulated with both of these approaches is well tolerated and immunogenic."
The investigators randomly assigned volunteers, aged 18-60 years, to receive two doses of a placebo or the whole-virus vaccine at 1.25µg, 2.5µg, 5µg, or 10µg doses plus the adjuvant aluminium hydroxide.
After 56 days they found that all the formulations produced antibodies against the virus but the best response was seen in the 10µg group after two doses.
The 10µg vaccine met all the European regulatory requirements for the licensing of an influenza vaccine.
Since a 30µg vaccine that needs to be given in two doses may only provide enough vaccine for 225m people under current manufacturing capabilities, a dose-sparing 10µg vaccine could significantly boost capacity.
It may be too early for vaccine manufacturers however to pop the champaign as the authors say more trials testing whole-virus H5N1 vaccine with adjuvant in larger numbers of individuals, including elderly and children, are needed.
In July GlaxoSmithKline announced it had developed a dose-sparing bird flu vaccine that enabled over 80 per cent of subjects who received 3.8µg of antigen in a trial to demonstrate a strong seroprotective immune response.
