New adjuvants on horizon for influenza vaccines

BOSTON — Several influenza vaccine adjuvants that have been used in Europe for many years may be incorporated into US vaccines soon, according to a presenter here at the IDSA 49th Annual Meeting.

Martin Friede PhD, who heads the Technology Transfer Team within the Department on Innovation, Information, Evidence and Research at the World Health Organization in Geneva, Switzerland, spoke about influenza vaccine adjuvants.

Adjuvants are added to vaccines to improve the immune response. They are known to increase antibody titers; reduce antigen dose (dose sparing for a pandemic); reduce the number of doses needed because they provide more rapid protection; enable immunization in patients with weakened immune systems; provide appropriate bias; and induce cell-mediated immunity, according to Friede.

“They are a critical enabling component for subunit/recombinant vaccines,” he said.

Adjuvants currently approved for global use include aluminum (alum); MF59 (squalene emulsion); AS03 (squalene/tocopherol emulsion); AF3 (squalene emulsion; Virosomes (liposomes)); and polyoxidonium (poly-electrolyte)).

Friede said alum adjuvants are widely used in pediatric vaccines — including DTP, Hepatitis B virus and pneumococcal vaccines — because they enhance titers and they have a long record of safety.

The drawback with alum adjuvants is that they are not really suitable for yearly administration because the adjuvant effect is dependent on many factors, according to Friede. He added that there are challenges that are specific for influenza, including that the antigens are variable and that the benefit for influenza vaccines is not convincing.

“Each year, the influenza antigen with aluminum changes and it is very different to make it consistent,” Friede said.

Despite its limitations, there are several influenza vaccines with alum — whole killed virion vaccines and split vaccines — that are approved for use around the world but not in the United States, according to Friede.

Oil-in-water emulsions are simply droplets of oil in water (~100 nm), the most common of which are squalene & tocopherol and tween & lecithin.

The MF59 adjuvant (Novartis) is made from squalene in water with Tween + Span and has been used in influenza vaccines in European countries since 1996. The push toward development of the MF59 adjuvant began with the last emergence of H5N1 because it required an enormously large dose of antigens needed to get an immune response.

“However, the moment you add oil and water, the immune results were enhanced enormously,” Friede said.

In 2009, when MF59 was incorporated into the 2009 H1N1 pandemic vaccine, it increased global vaccine production capacity to more than 200 million doses distributed for all ages.

The caveat is that there is an increase in local reactogenicity, according to Friede.

“You cannot have an omelet without breaking the eggs,” Friede said. “The influenza vaccine with this adjuvant often results in some local site reactions and some redness, but it’s nothing serious.”

Friede said that something to keep in mind is that as the child grows older, the response to the vaccine without the adjuvant becomes better, but all the children responded, even the youngest.

For infants aged 6 months to 5 years, receiving H1N1 (seasonal) plus oil and water resulted in a 96% seroconversion to seasonal strain and a 2% seroconversion to H1N1. As for adults, 5 % to 22% seroconversion to H1N1 v with unadjuvanted seasonal vaccine.

“I would say to stay tuned because you may have an influenza vaccine with this adjuvant available in your country soon,” Fried said. — by Cassandra A. Richards

Disclosure: Dr. Friede reports no relevant financial disclosures.

For more information:

• Friede M. Symposium 15. Presented at: IDSA 49th Annual Meeting. Oct. 20-13, 2011. Boston.

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