Characterization of the early cellular immune response induced by HPV vaccines

Abstract

IntroductionCurrent human papillomavirus (HPV) vaccines consist of virus-like particles (VLPs) which are based on the L1 protein, but they are produced by different expression systems and use different adjuvants. We performed in-depth immunophenotyping of multiple innate and adaptive immune cells after vaccination with bivalent versus nonavalent HPV vaccines.MethodTwenty pre-menopausal HPV-seronegative women were enrolled and randomized to receive three-doses of either the bivalent or the nonavalent HPV vaccine. Blood samples were collected at multiple time points from baseline up to 7 months after first vaccination. Four extensive EuroFlow flow cytometry antibody panels were used to monitor various immune cell subsets. Additionally, HPV-specific memory B- and T cells were determined by ELISPOT and HPV-specific antibody levels were measured by a VLP-based multiplex immunoassay.ResultsIn both cohorts, the numbers of plasma cells expanded in the first week after both primary and tertiary vaccination. HPV16 and HPV18-specific antibody levels and memory B and T-cell responses were higher in the bivalent than in the nonavalent vaccinees one month post third vaccination. For HPV31 and HPV45-specific antibody levels this pattern was reversed. Monocytes showed an expansion one day after vaccination in both cohorts but were significantly higher in the bivalent vaccine cohort. Large heterogeneity in responses of the other cell subsets was observed between donors.ConclusionThis pilot study showed a consistent response of monocytes and plasma cells after vaccination and a considerable variation in other circulating immune cells in both types of HPV vaccines between donors.

Immune response following a two-dose schedule of bivalent HPV vaccination among girls and boys

“…Earlier studies found that local immune responses (antibodies at the site of entry) should be considered. Type specific and cross-reactive HPV antibodies are important in the protection against disease but are only a part of the immunological compartment, as cellular-, innate-and mucosal immunity also play a role (27).…”

Scientific approaches toward improving cervical cancer elimination strategies

“…The steady antibody responses induced by the HPV vaccines are a result of sustained production by plasma cells, largely afforded through the generation and maintenance of strong memory B cell activation. HPV‐specific memory B cell responses are induced early upon vaccination 53 and may remain quiescent for long periods until readily recalled following antigen (re)exposure. Sustained immune responses induced upon vaccination are critically impacted by the number and timing of vaccine doses, but pertinent data on the effect of doses in HPV vaccine‐induced B‐cell response is currently scarse and challenging to interpret due to discrepancies in cohort ages 54 despite the strong evidence supporting an optimal memory B cell response in children aged 9–13 years 55 .…”

Performance of spectral flow cytometry and mass cytometry for the study of innate myeloid cell populations

“…Two antibody panels specifically designed for the study of IMC populations were used to stain PBMC, based on previous reports (EuroFlow patent "Means and methods for multiparameter cytometry-based leukocyte subsetting"; PCT/NL2020/050688, priority date 5 November 2019) (27,(32)(33)(34)(35)(36). Briefly, the selection of the markers employed in both MC and SFC combinations was performed based on unbiased identification of the most optimal set of markers to identify each population, in order to provide the best population discrimination and avoid any type of redundancy (27, 37-41).…”