Sex-Specific Differences in Cytokine Induction by the Glycolipid Adjuvant 7DW8-5 in Mice

7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-γ and increasing protective CD8⁺ T cell responses. The addition of 7DW8-5 was previously shown to improve the efficacy of a CD8⁺ T cell-mediated heterologous 'prime-and-trap' malaria vaccine against Plasmodium yoelii sporozoite challenge in inbred female mice. Here, we report significant differential sex-specific responses to 7DW8-5 in inbred and outbred mice. Male mice express significantly less IFN-γ and IL-4 compared to females following intravenous 7DW8-5 administration. Additionally, unlike in female mice, 7DW8-5 did not improve the vaccine efficacy against sporozoite challenge in prime-and-trap vaccinated male mice. Our findings highlight the importance of including both female and male sexes in experimental adjuvant studies.