Abstract
Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses.
Highlights
The quadrivalent human papillomavirus (HPV) vaccine provides near-complete protection against sexually transmitted HPV infections that most commonly cause anogenital and oropharyngeal cancers (HPV types 16 and 18) and genital warts (HPV 6 and 11) when administered to individuals naive to these types [1,2,3,4,5,6]
We chose psV as our ‘bait’ Ag because they contain the vaccine Ag in a polyvalent geometry that closely resembles the vaccine virus-like particles (VLPs) [19], and because they could be evaluated for proper folding and function following Alexa Fluor 488 (AF488)-conjugation, using a reporter-based neutralization assay [20]
In order to characterize Bmem elicited by the quadrivalent HPV (qHPV) vaccine, we first needed to establish an Ag-labeling method to identify qHPV-specific Bmem
Summary
The quadrivalent HPV (qHPV) vaccine provides near-complete protection against sexually transmitted HPV infections that most commonly cause anogenital and oropharyngeal cancers (HPV types 16 and 18) and genital warts (HPV 6 and 11) when administered to individuals naive to these types [1,2,3,4,5,6]. No correlate of protection has been confirmed for the qHPV vaccine due to low numbers of disease cases in vaccinees [7], passively transferred immune sera have been shown to be sufficient for protection against papillomavirus challenge in a number of animal models [8,9,10]. There is evidence that qHPV vaccination elicits plasma cells, which help sustain antigen (Ag)-specific Ab levels over time by secreting Ab for extremely long periods; and memory B cells (Bmem), which renew
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