INTRODUCTION: This thesis investigates B cell and T follicular helper cell (Tfh) responses elicited by Gardasil 9 HPV vaccination as key drivers of long-term antibody-mediated protection and hence vaccine efficacy. The research was performed within a randomised clinical trial that aimed to compare antibody responses between one and two doses of Gardasil 9 given to 4 to 8- and 9 to 14-year-old females with reference to three doses given to 15 to 26-year-olds. METHODS: ELISpot and FluoroSpot assays were used to enumerate HPV 16 and HPV 18 specific IgG memory B cells and IgG and IgM plasma cells, respectively. An activation-induced marker flow cytometry assay was used to identify HPV 16 and HPV 18 specific Tfh cells following in-vitro stimulation with respective virus-like particles. The frequencies of total IgG and IgM plasma cells, and ex vivo activated Tfh cells in circulation were measured using flow cytometry. HPV 16 specific B cell repertoire was mapped by first sorting single HPV 16 specific memory B cells using fluorescently labelled HPV 16 virus-like particles and subsequently sequencing the naturally paired B cell receptor heavy and light chains using arm-iPair technology. HPV specific antibody titers were measured commercially using a Competitive Luminex Inhibition assay. The effects of age and dose number on vaccine-induced immune responses were evaluated. RESULTS: Frequencies of HPV 16 and HPV 18 specific plasma cells, memory B cells and Tfh cells were generally low after the first vaccination dose across all three age groups. A robust boosting of all responses was observed following the second or third vaccination dose which tended to be higher in the younger age groups, except the in vitro activated Tfh cell response which increased modestly in the youngest age group. Both 2- and 3-dose vaccination schedules induced high HPV 16 and HPV 18 specific IgG antibody titers which increased with decreasing age. There was a strong positive correlation between antibody titers and plasma cells which was not observed upon comparing the antibody titers with memory B cells and Tfh cells. HPV 16 specific B cell repertoire was enriched for diverse germline heavy and light chain variable and junctional gene variants and utilized unique complimentary determining region 3 (CDR3) of variable amino acid lengths. CONCLUSION: The B cell and Tfh cell responses induced by HPV vaccination at variable magnitudes by age and dose may be responsible for the similar trends observed on subsequent antibody responses. This study provides insights on the possible roles played by these cell responses in shaping short- and long-term vaccine protection. Additionally, the low cellular response induced from the first vaccination dose may indicate a potential impact of single dose vaccination that should vaccine immunogenicity wane, low responders may be at risk of acquiring new infections and developing cancer, hence, the immunogenicity induced by single dose vaccination requires keen monitoring. The higher immunogenicity observed in the youngest age group highlights a need to further explore vaccination of children aged below 9 years in which HPV vaccination has not been tested previously.