Abstract
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.
Data availability
All data supporting the findings of this study are contained within the article and its supplementary content. The raw data can be obtained from the corresponding author upon request.
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Acknowledgements
The authors thank the study participants and their families for their valuable contributions to this research and Medical Research Council Unit The Gambia at The London School of Hygiene and Tropical Medicine immunology platform, research support and training departments for availing research facilities. Work funded by Medical Research Council (UK), Wellcome Trust and UK Department for International Development (grant MC_EX_MR/N006070/1 to E.C.), Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine Doctoral Training fellowship (2018/2019 to E.W.K.) and Wellcome Institutional Strategic Support Fund (grant 204928/Z/16/Z to M.J.H. and E.C.).
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Conceptualisation: E.C., E.W.K., S.R., M.R.G., A.O.B., D.O.A. and M.J.H. Methodology: E.C., E.W.K., S.R., M.R.G., M.J.H., D.O.A., A.O.B., L.D., T.J., F.K., O.J., J.L., A.S.P., S.B. and M.N.J. Investigation: E.C., E.W.K., S.R., A.O.B., M.R.G., M.J.H., D.O.A., L.D., T.J., F.K., S.B., O.J., J.L. and A.S.P. Visualisation: E.W.K., E.C., M.R.G., A.O.B., M.J.H., D.O.A., L.D., T.J., F.K., O.J., J.L., A.S.P. and M.N.J. Funding acquisition: E.C., M.J.H. and E.W.K. Project administration: M.N.J., J.L., S.B., D.O.A., A.O.B., S.R. and E.W.K. Supervision: E.C., S.R., M.R.G., E.W.K. and M.J.H. Writing—original draft: E.W.K., E.C., M.R.G., A.S.P. and D.O.A. Writing—review & editing: E.W.K., E.C., M.R.G., M.J.H., D.O.A., A.O.B., S.R., J.L., M.N.J., L.D., S.B., T.J., F.K., O.J. and A.S.P.
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Kiamba, E.W., Ajiboye, D.O., Bashorun, A.O. et al. Plasmablast, memory B cell and T follicular helper cell responses after human papillomavirus vaccination: effect of dose number and age. npj Vaccines (2026). https://doi.org/10.1038/s41541-026-01408-w
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DOI: https://doi.org/10.1038/s41541-026-01408-w
