A whole-virion vaccine for the H5N1 avian influenza virus produces acceptable levels of immunity even at low doses, researchers found in a preliminary study.
The vaccine, developed at the Sinovac Biotech Co. in Beijing, seems to be effective when delivered in two 10-mcg doses 28 days apart. A different whole-virion vaccine required two 90-mcg doses, and a split-virion vaccine required two 30-mcg doses.
Given current manufacturing constraints, supplies of that split-virion vaccine would be limited to about 225 million people, far lower than worldwide demand in the event of an avian flu pandemic. A much greater number of people could be treated if the new dosage-sparing vaccine is found effective in larger clinical trials.
Dr. Jiangtao Lin of the Chinese-Japanese Friendship Hospital, Beijing, and colleagues reported on a placebo-controlled, double-blind, phase I trial of 120 volunteers aged 18–60 years. The participants were given either two injections of placebo or two injections of an inactivated, whole-virion influenza A (H5N1) vaccine at four doses between 1.25 mcg and 10 mcg. Aluminum hydroxide was added as an adjuvant, a practice previously shown to reduce the dosage needed to produce immunogenicity.
Although all four doses produced immune responses, the 10-mcg dose produced 78% seropositivity, significantly higher than that produced by the other doses (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69294–5]).
No serious adverse events were reported at any dose level up to 56 days after the first injection. Local and systemic reactions were all rated as mild and transient. Pain at the injection site in the deltoid muscle was more frequently reported in the vaccine groups than in the placebo group, but there were no significant differences in systemic reactions, the most common of which were fever, headache, myalgia, and nausea.
In an accompanying editorial, Dr. Iain Stephenson, of the Leicester (England) Royal Infirmary, noted that vaccination will be central to any response to an avian flu pandemic (Lancet 2006 Sept. 7 [Epub DOI:10.1016/S0140–6736(06)69340–9]). The 1918 influenza pandemic—also derived from an avian virus—caused up to 50 million deaths. Dr. Stephenson said that the dose-sparing approach described by Dr. Lin could be crucial for obtaining a global supply of the vaccine.
He also noted that earlier whole-virion vaccines were associated with febrile reactions, especially in children. Although larger clinical trials will be necessary before widespread immunization, Dr. Stephenson said a modest amount of reactogenicity might be acceptable in the face of the threat of a global pandemic.
The authors of the study acknowledged that funding came from the Sinovac Biotech Co., which had a role in both study design and monitoring. They said the company had no role in data collection or in writing the report.