Scaffold Vaccines for Generating Robust and Tunable Antibody Responses

Abstract Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities to control the resulting subclasses of antibodies produced, which can mediate effector functions relevant to distinct disease settings. Here, it is found that three scaffold‐based vaccines, fabricated from poly(lactide‐ co ‐glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce robust, long‐term antibody responses to a model peptide antigen gonadotropin‐releasing hormone with single‐shot immunization. Compared to a bolus vaccine, PLG vaccines prolong germinal center formation and T follicular helper cell responses. Altering the presentation and release of the adjuvant (cytosine‐guanosine oligodeoxynucleotide, CpG) tunes the resulting IgG subclasses. Further, PLG vaccines elicit strong humoral responses against disease‐associated antigens HER2 peptide and pathogenic E. coli , protecting mice against E. coli challenge more effectively than a bolus vaccine. Scaffold‐based vaccines may thus enable potent, durable and versatile humoral immune responses against disease.