Vaccination remains the most cost-effective method for preventing infectious diseases. Key to vaccine design is the development of immunological memory, which is an essential property of the adaptive immune system. Bacterial polysaccharide conjugate vaccines are the gold standard currently used to confer protection of the host by inducing humoral immune responses against T-cell-independent antigens. Conjugate vaccines are effective, but we propose that local mucosal immune responses are likely to also play an important role in inducing immunity, and they have been less explored than systemic and adaptive immune responses. Adjuvants have been used to improve the immune response to vaccine antigens, however, no mucosal adjuvant has been licensed for human use. Here we describe the recent progress in the use of mucosal adjuvants to achieve significant immune responses against T-cell-independent antigens. We also introduce the idea that studying the mechanisms that induce cell sub-populations with strong immunological memory may facilitate the design of novel vaccine formulations, in particular in cases of B-cell unresponsiveness to thymus-independent stimuli.