Adjuvant vaccines not only promote a better immune response but can reduce the amount of virus needed for production of a vaccine, which could be an important factor during a pandemic when greater supplies of vaccines are required.

Those issues were raised in 2013 when the FDA approved Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, for avian flu. It was the first adjuvanted influenza vaccine approved by the Agency. The vaccine was licensed for adults 18 years of age and older who are at increased risk of exposure to the H5N1 influenza virus subtype contained in the vaccine.  

Vaccine development. Source: Getty

“Adults aged 65 years and older are at the greatest risk of serious complications from influenza compared with young, healthy adults because the immune system weakens with age,” William Schaffner, MD, medical director at the National Foundation for Infectious Diseases and professor of Medicine and Preventive Medicine at Vanderbilt University, Nashville, said at the time. “The approval of an adjuvanted trivalent influenza vaccine provides a new vaccine alternative.”

Two years later, the FDA approved FLUAD, a standard-dose, trivalent inactivated flu vaccine that contains an adjuvant and is licensed only for use seasonally for adults 65 and older.

While both vaccines contain adjuvants, there are some differences. FLUAD is formulated with the adjuvant MF59 to help create a stronger immune response to vaccination. MF59 is an oil-in-water emulsion of squalene oil, which is a naturally occurring substance found in humans, animals and plants and is purified for the vaccine manufacturing process, as well as two surfactants.

The AS03 adjuvant is an oil-in-water emulsion composed of squalene but also includes polysorbate 80 and α-tocopherol, i.e. vitamin E. AS03 was first used in a prepandemic H5N1 vaccine and was subsequently included in two influenza A(H1N1)pdm09 pandemic vaccines.

A new study published in the journal Vaccine noted that oil-in-water adjuvants improve pandemic influenza vaccine efficacy, but research is lacking on AS03 vs. MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines.

University of New South Wales-led researchers conducted an indirect-comparison meta-analysis comparing the two adjuvants. To do that, they reviewed published data from randomized controlled trials in literature databases from January 2009, to September 2018, searching for evaluations of the immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. 

Comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant vs. unadjuvanted counterparts were conducted, followed by indirect contrast of different AS03 vs. MF59 regimens.

Used in the meta-analysis were 22 published articles with a total of 10,734 participants.

Results indicated that, for adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR vs. unadjuvanted vaccines (all four comparisons); MD = 0.56 (95% CI, 0.33-0.8) to 1.18 (95% CI, 0.72-1.65). 

MF59 (full-dose)-adjuvanted vaccines (7.5 µg haemagglutinin) were found to be superior to unadjuvanted vaccines (three of four comparisons); MD = 0.47 (95% CI, 0.19-0.75) to 0.80 (95% CI, 0.44- 1.16). 

“Adult indirect comparisons favored AS03 over MF59 (six of eight comparisons; P < 0.001 to P = 0.088),” the researchers wrote. “Pediatric indirect comparisons favored MF59-adjuvanted vaccines (two of seven comparisons; P = 0.011, 0.079). However, unadjuvanted control group seroconversion rate was lower in MF59 than AS03 studies (P< 0.001 to P = 0.097).”

The study team pointed out substantial heterogeneity and that adult AS03 studies had lower risk of bias.