 Advances in genomic sequencing have made it easier than ever before to design safe and simple vaccines, but there is still an urgent need to improve vaccine technology, specifically for adjuvants, the immunostimulatory molecules that are added along with the target antigens for full disease protection. Recent research suggests that in addition to boosting the vaccine's immune response, adjuvants may be able to shape the specific immune responses, which could be very helpful in fighting tricky pathogens. But so far, scientists have not studied combinations of adjuvants and antigens in any rigorous way, making comparisons difficult. To fill this gap, an international team of immunologist and infectious disease specialists tested five adjuvants in mice, along with antigens from either tuberculosis, influenza, or chlamydia. Each of these diseases is best fought off with a different combination of immune responders from various types of T-cell help to a strong antibody response from B-cells. The researchers used a standardized protocol and immunized mice three times at three-week intervals, then evaluated the immune responses and assessed the efficacy. The team found that regardless of the antigen used, each adjuvant showed a unique immunological signature. For example, in all disease models, the classic vaccine addition, ALAM, increased antibody titers, whereas MF-59 provided a strong antibody response along with a burst of interleukin-5. GLA-SE added a strong TH-1 response, while CAF-01 produced a mix of TH-1 and TH-17. IC-31 focused on TH-1. Ultimately, some adjuvants were better for certain diseases than others. MF-59 and GLA-SE were great for influenza, while GLA, CAF-01, and IC-31 were especially good at protecting against TB and chlamydia. The findings suggest that adjuvants have the potential to target different diseases and should be carefully considered during vaccine design. This first of its kind study provides an important glimpse into the types of responses that certain adjuvants can direct and shows how this information could be used to shape the next generation of vaccines.