Plasmablast, memory B cell and T follicular helper cell responses after human papillomavirus vaccination: effect of dose number and age

Multiple doses of HPV vaccines induce durable, antibody-mediated protection against HPV infections and HPV-associated diseases. Although actual protection against disease by a single HPV vaccination dose has not been confirmed in randomised trials, this regimen induces protection against incident and persistent HPV infection, similar to multi-dose schedules. However, the cellular mechanisms driving durable antibody responses to subunit vaccines remain poorly understood. B cells and T follicular helper (Tfh) cells play central roles in long-term antibody-mediated immunity. We characterised plasmablast, memory B cell (Bmem), and Tfh cell responses to assess the effects of dose number and age following HPV vaccination in Gambian females aged 4–26 years. A significant induction of HPV16/18-specific IgM plasmablasts occurred after the first dose, while robust HPV16/18-specific IgG plasmablast, Bmem, and Tfh responses were observed after two or three doses. Activation within the total Tfh pool increased with decreasing age, whereas HPV16/18-specific Tfh activation was higher in older vaccinees. These findings demonstrate the potential of multi-dose HPV vaccination schedules to sustain antibody protection through coordinated B cell and Tfh responses and highlight the need for continued monitoring of single-dose regimen. Exploring HPV vaccination in children under nine years may improve delivery and uptake.