Antigen Sparing Adjuvant Strategy Might Increase Avian Flu Vaccine Production

There is a strategy which could significantly boost the production of the avian influenza vaccine, allowing many more people to be vaccinated, according to an article in The Lancet. Professor Geert Leroux-Roels, Centre for Vaccinology, Ghent University and Hospital, Belgium and team said that if they combine the vaccine with an oil-in-water emulsion (adjudant) the body is able to produce six times as many avian flu neutralizing antibodies, compared to what the body can produce with a non-adjuvanted vaccine with an identical dose.


Several scientists and health care experts agree that when the next global flu pandemic happens it will most likely be caused by the H5N1 bird flu virus strain. H5N1 contains an H5 hemagglutini antigen subtype, which often produces a weak immunogenic response in human beings. Most of the world is immunologically naГЇve to H5 hamagglutinin antigen subtypes (have very little or no immunity). Therefore, a one dose schedule, which is usually enough for a normal human flu vaccine, most likely will not be enough to give adequate immunity. "Clearly, new formulations that require less antigen per dose are needed. The use of adjuvant to improve immunogenicity is a crucial antigen-sparing strategy," the authors write.


The scientists studied 400 volunteers, they had been divided into eight groups and were aged 18-60. Four antigen doses were studied - 3.8 Ојg, 7.5 Ојg, 15 Ојg and 30 Ојg haemagglutinin. Some were given doses with and some without the oil-water adjuvant. Their immune responses were analyzed through blood tests. The researchers found that the adjuvanted formulations were much more immunogenic than the non-adjuvanted ones, across all doses. Good safety profiles were also found among all eight vaccine formulations. There were more injection-site symptoms and general symptoms from the adjuvant vaccines, which were mainly mild to moderate and transient.


The fact that the 3.8 Ојg adjuvanted vaccine dose induced cross-immunity against the clade two* H5N1 Indonesia strain in over 75% of the patients with neutralizing titres which are six times higher than the non-adjuvanted formulation represent a "significant antigen sparing that could increase the number of recipients of the pandemic influenza vaccine."


"The cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed before pandemic outbreak, which is an important mitigation strategy proposed for pandemic influenza," the authors conclude.


"Leroux-Roels and colleagues' study is the first to show significant antigen dose-sparing, high levels of immunogenicity in association with a novel adjuvant, and the induction of cross-clade immunity against A/H5N1 viruses. Their study lends support for considering a strategy of immunising some groups with prepandemic vaccines for preparedness in the event of a pandemic from an H5N1 virus. This vaccine appears to be an important step forward in our ability to protect against the pandemic threat posed by highly pathogenic influenza A/H5N1 viruses,", Dr Suryaprakash Sambhara, CDC, Atlanta, Georgia, and Dr Gregory Poland, Mayo Clinic and Foundation, Minnesota, wrote in an accompanying Comment.


*The H5N1 virus has diverged into three distinct categories or clades (1, 2, and 3), of which clade 2 has multiple sub-clades.


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