The benefits of adjuvants for enhancing vaccine immunogenicity and efficacy are well known. Numerous novel adjuvants are at advanced levels of characterization, including some in clinical trials. However, understanding the relative benefits of each is hindered by a lack of comparative studies between adjuvants within the same study. To address this, we have performed a side-by-side comparison of 5 novel combination adjuvants (Alhydroxyquim-II, T-VANT, TRAC-478, IVAX-1 and IVAX-3) by formulating each with two approved seasonal influenza vaccines, Flublok® and Fluzone HD®, and assessing immunogenicity and efficacy in female and male C57Bl/6 mice. Although all tested adjuvants were immunogenic and protective against H1N1 challenge, T-VANT, TRAC-478 and IVAX-1 and -3 were associated with systemic inflammatory cytokines and robust Th1 responses, while Alhydroxyquim-II elicited lower levels of inflammatory cytokines and a Th2 response. Greater morbidity after challenge was also detected in males compared to females. Side-by-side comparisons of existing and novel adjuvants with the same antigen and model system will help inform rational adjuvant selection and guide vaccine development for influenza and other infectious diseases.
© 2026. The Author(s).