Adjuvants enhance protective antibodies against seasonal influenza viruses following a single vaccination of Fluzone

Fluzone is a commercial, split-inactivated influenza virus vaccine produced from embryonated chicken eggs and administered via intramuscular injection. One strategy to increase the potency of this vaccine is to formulate with an effective adjuvant. To address this goal, mice were vaccinated with Fluzone mixed with either squalane oil-in-water adjuvant (Addavax) or a combination of a synthetic toll-like receptor (TLR) 4 and TLR7/8 agonist (TRAC478). Mice vaccinated with vaccine plus adjuvant had higher anti-HA binding antibodies and hemagglutination-inhibition (HAI) titers than mice administered unadjuvanted vaccine following a single vaccination. In general, mice vaccinated with Fluzone plus TRAC478 had higher HAI and neutralizing titers after the first vaccination compared to mice vaccinated with Fluzone plus Addavax. All vaccinated mice challenged with an H1N1 influenza virus (A/Brisbane/02/2018) lost little weight and survived challenge. Mice vaccinated with Fluzone plus either adjuvant had no detectable lung viral titers at day 3 post-challenge. Mice vaccinated with unadjuvanted Fluzone or mock vaccinated mice had 3-5 log higher viral titers. Vaccinated mice challenged with an H3N2 influenza virus (A/Switzerland/9715293/2013) lost, on average, 10-15 % of their original body weight by day 3 post-challenge but slowly recovered with viral lung titers that were 2-2.5 logs lower than mice administered unadjuvanted Fluzone. Lungs collected from mice vaccinated with Fluzone plus TRAC478 had low levels of lung infiltrating cells following a single vaccination. Overall, the use of adjuvant, particularly TRAC478, enhanced the elicitation of protective antibodies elicited by Fluzone following a single vaccination.