A Single Human Papillomavirus Vaccine Dose Improves B Cell Memory in Previously Infected Subjects

•Five women with naturally elicited human papillomavirus (HPV) 16 antibodies (Abs) were given a single HPV vaccine dose.•Vaccination boosted anti-HPV Ab levels, memory B cell numbers, and frequency of neutralizing Abs cloned from memory B cells.•Therefore, HPV vaccine augments natural immunity to HPV.Persons infected with oncogenic human papillomavirus (HPV) types may remain susceptible to re-infection despite eliciting immune responses to HPV. It is unclear whether licensed HPV vaccines can provide additional immunologic benefit to these persons. To investigate this question, the B cell memory of five previously infected subjects was examined before and after they received an HPV vaccine dose. Vaccination increased HPV-specific antibody and memory B cell levels. We also found more antibodies cloned from post-vaccination, HPV-specific memory B cells were potently neutralizing than those cloned from pre-vaccination cells. These results show vaccination augments natural HPV immunity in previously infected subjects.

Although licensed human papillomavirus (HPV) vaccines are most efficacious in persons never infected with HPV, they also reduce infection and disease in previously infected subjects, indicating natural immunity is not entirely protective against HPV re-infection. The aim of this exploratory study was to examine the B cell memory elicited by HPV infection and evaluate whether vaccination merely boosts antibody (Ab) levels in previously infected subjects or also improves the quality of B cell memory. Toward this end, the memory B cells (Bmem) of five unvaccinated, HPV-seropositive subjects were isolated and characterized, and subject recall responses to a single HPV vaccine dose were analyzed. Vaccination boosted Ab levels 24- to 930-fold (median 77-fold) and Bmem numbers 3- to 27-fold (median 6-fold). In addition, Abs cloned from naturally elicited Bmem were generally non-neutralizing, whereas all those isolated following vaccination were neutralizing. Moreover, Ab and plasmablast responses indicative of memory recall responses were only observed in two subjects. These results suggest HPV vaccination augments both the magnitude and quality of natural immunity and demonstrate that sexually active persons could also benefit from HPV vaccination. This study may have important public policy implications, especially for the older ‘catch-up’ group within the vaccine's target population.