Antigen Sparing Strategy Could Boost Bird Flu Vaccine Production

Professor Geert Leroux-Roels, Centre for Vaccinology, Ghent University and Hospital, Belgium and colleagues report on an “antigen sparing adjuvant strategy”, which, by combining the vaccine with an oil-in-water emulsion “adjuvant”, allows the body to produce up to six times as many bird influenza virus neutralising antibodies as it would with an non-adjuvanted vaccine with the same dose.

The bird flu strain H5N1* is widely regarded as the probable cause of the next global influenza pandemic. This virus contains a H5 haemagglutinin antigen subtype, which generally produces a poor immunogenic response in humans and to which most of the world population is immunologically naïve. As a result, the one-dose schedule routinely used for seasonal “regular” influenza vaccines is unlikely to be sufficient to give immunity. The authors say: “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 researchers did a study of eight groups of 50 volunteers aged 18-60 years, and studied four antigen doses (3.8µg, 7.5µg, 15µg, 30µg haemagglutinin) given with or without the oil-water adjuvant. Blood samples were then collected to analyse the immune response, and the results showed that the adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all doses. All eight vaccine formulations had good safety profiles, although the adjuvanted vaccines produced more injection-site symptoms and general symptoms (most of which were mild to moderate and transient) than the non-adjuvanted vaccines.

The authors say that the ability of the 3.8µg dose of the adjuvanted vaccine to induce cross-immunity against the clade two* H5N1 Indonesia strain in more than the three-quarters of individuals with neutralising titres which are six times higher than the non-adjuvanted formulation “represents significant antigen sparing that could increase the number of recipients of the pandemic influenza vaccine.”

They conclude: “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.”

In an accompanying Comment, Dr Suryaprakash Sambhara, Centers for Disease Control and Prevention, Atlanta, Georgia, USA and Dr Gregory Poland, Mayo Clinic and Foundation, Minnesota, USA, say: “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.”

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