Abstract
Human papillomavirus virus (HPV) vaccines aim to provide durable protection and are ideal to study the association of cellular with humoral responses. We assessed the duration and characteristics of immune responses provided by the quadrivalent HPV (4vHPV) vaccine in healthy female adults with or without prior exposure with type 16 and 18 HPV. In a prospective cohort, vaccine naïve females received three doses of 4vHPV vaccine and were followed for two years to assess cellular (intracellular cytokine staining, proliferation and B cell ELISpot assays) and humoral (multiplex L1/L2 viral-like particles (VLP) and M4 ELISAs) responses. Frequencies of vaccine-specific CD4+ T cells correlated with antibody responses. Higher HPV antibody titers were found at all time points in participants previously exposed to HPV, except for anti-HPV-18 at Day 187 (one week post the third vaccination). Retrospective cohorts enrolled females who had previously received two or three 4vHPV doses and tested antibody titers by M4 ELISA and pseudovirion neutralization assay along with memory B cells (MBCs). Almost all women enrolled in a retrospective cohort with two prior doses and all women enrolled in a retrospective cohort with three prior doses had sustained antibody and memory responses. Our findings indicate that HPV vaccination induces a long-lasting, robust cellular and humoral immune responses.
Highlights
Human papillomaviruses (HPV) types 16 and 18 are the most important high-risk Human papillomavirus virus (HPV) types, causing approximately 70% of cervical cancers worldwide
We enrolled a total of 203 female subjects for the three studies, 47 in the prospective cohort, 78 in the Retro 2 cohort, and 78 in the Retro 3 cohort (Table 1 and Figure 1)
Our study comprehensively evaluated the immunological response to three doses of 4vHPV
Summary
Human papillomaviruses (HPV) types 16 and 18 are the most important high-risk HPV types, causing approximately 70% of cervical cancers worldwide. When administered as three-dose schedules, these vaccines demonstrated high vaccine efficacy (>96%) against cervical cancer precursors in HPV-naïve individuals and induced high levels of type-specific antibodies that persist for over nine years [1,2,3,4,5,6]. The high immune responses and effectiveness of the HPV vaccines led the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA) to revise their recommendations in 2016 from administering three doses of HPV vaccine over six months to two doses given 6–12 months apart for individuals younger than 15 years of age [7,8] after studies found non-inferior antibody (Ab) responses with reduced-dose. HPV vaccines have been found to induce herd immunity after the introduction of national programs, with significant declines in the prevalence of vaccine-type virus both in vaccinated and unvaccinated women [9,10]
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