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

HPV vaccines induce durable, antibody-mediated protection against HPV infections and HPV-associated diseases, including cervical cancer, other anogenital and oropharyngeal cancers, and genital warts even after a single vaccine dose. However, the underlying cellular mechanisms driving these robust and long-lasting antibody responses to subunit vaccines remain poorly understood. B cells and T follicular helper (Tfh) cells play central roles in establishing long-term antibody-mediated immunity. We characterized 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. Our results show a significant induction of HPV16/18-specific IgM plasmablasts after the first vaccine dose, and robust HPV 16/18-specific IgG plasmablast, Bmem, and Tfh cell responses after two doses in 4-14-year-olds and three doses in 15-26-year-olds. HPV 16/18-specific plasmablast and Bmem responses were generally higher in younger age groups. Ex vivo activation within the total Tfh cell pool also increased with decreasing age, whereas HPV 16/18-specific Tfh cell 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 cell responses, while underscoring the need for active monitoring of single-dose HPV vaccination strategies currently being implemented. Furthermore, exploring HPV vaccination in children under nine years of age could simplify vaccine delivery logistics and improve global uptake.