Germinal center enhancement by extended antigen availability

Vaccine elicitation of protective antibody responses has proved difficult for a number of important human pathogens, including HIV-1. The amount of somatic hypermutation associated with the development of broadly neutralizing antibodies against HIV has not been achieved using conventional immunization strategies. An underexplored aspect of vaccine design is modulation of antigen kinetics. Immunization strategies with extended antigen availability have recently been shown to enhance humoral responses. In this review, we explore the mechanisms through which sustained antigen availability can enhance germinal center responses and the potency of antibody responses. These potential mechanisms include shifting B cell recognition away from non-neutralizing immunodominant epitopes, altered kinetics of immune complex deposition, improved T follicular helper (Tfh) cell responses, enhanced affinity maturation, and enhanced development of B cell memory. Finally, we discuss immunization strategies that result in extended antigen availability.