We assessed antibody persistence and the impact of an additional dose administered 42-60 months after initial vaccination. Girls initially vaccinated at ages 9-10 with two doses of quadrivalent HPV vaccine participated in two randomized trials: The 0-6-42HPV study which compared a quadrivalent and bivalent additional dose given at 42 months; The 0-6-60ICI-VPH study compared no additional dose to a quadrivalent dose at 60 months. HPV16/18 antibody detection and geometric mean concentrations (GMCs) were assessed (M9ELISA). Overall, 526 girls provided a blood sample. All had detectable HPV16/18 antibodies 10 years post-initial vaccination. An additional dose at 42 versus 60 months led to similar GMCs, both with higher immune responses compared to 2-dose group participants. Compared to the quadrivalent, the bivalent induced significantly higher HPV18 GMCs, which has unknown clinical significance. Two-dose schedule and delayed quadrivalent or bivalent additional doses are highly immunogenic, supporting long-term immunogenicity of alternative and mixed vaccination schedules.

BACKGROUND:Following up on previously published short-term findings, we assessed the persistence of the immune response at 36 months following mixed-HPV vaccination schedules using one nonavalent (9vHPV) dose and one bivalent (2vHPV) dose (administered interchangeably) compared to a homologous two-dose 9vHPV schedule. METHODS:Girls and boys aged 9-10 years were randomized (1:1) to receive (I) two doses of 9vHPV (n = 168 according-to-protocol (ATP)) or (II) a mixed schedule (n = 169 ATP) of 2vHPV + 9vHPV (n = 86) or 9vHPV + 2vHPV (n = 83) with a 6-month interval. The proportion of participants with detectable antibodies and geometric mean concentrations (GMCs) for HPV types 6/11/16/18/31/33/45/52/58 were measured using M9ELISA at 7 and 36 months after the first dose. RESULTS:Antibodies to HPV16 and HPV18 persisted in all 337 participants (100%) at 36 months. Antibodies to the other 9vHPV-targeted types were detectable in 94-100% of participants vaccinated with a mixed schedule versus 100% for those vaccinated with a 2-dose 9vHPV schedule. GMCs for HPV16 and HPV18 were significantly higher in those vaccinated with a mixed schedule (9vHPV + 2vHPV and 2vHPV + 9vHPV) compared to the 9vHPV + 9vHPV schedule: 184.6 (145.5-234.3) and 151.7 (121.2-189.8) vs 97.7 (83.6-114.1) for HPV16, and 70.4 (53.5-92.7) and 72.7 (57.0-92.8) vs 40.3 (34.9-46.6) for HPV18. Additionally, the 9vHPV + 2vHPV mixed schedule resulted in higher GMCs when compared to the 2vHPV + 9vHPV schedule. GMC ratios (homologous/mixed schedules) decreased for HPV types not included in the bivalent vaccine, indicating that differences observed at 7 months were reduced at 36 months. Sex-stratified analyses showed no substantial differences between boys and girls. CONCLUSION:Serological responses of mixed-HPV vaccination schedules are sustained for at least 36 months post-vaccination and comparable to a 2-dose 9vHPV schedule, for HPV16/18. These findings provide immunogenicity evidence supporting the feasibility of mixed 2-dose HPV schedules, while further research on clinical effectiveness and implementation is needed to inform policy decisions. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov (NCT02567955).

Standardized measurement and reporting of antibody (Ab) levels induced by human papillomavirus (HPV) vaccination are essential for evaluating immunogenicity data across HPV vaccine trials and serosurveillance studies. The Frederick National Laboratory for Cancer Research generated an HPV serology standard for normalizing assays measuring antibodies to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. A study was conducted with the aim to calibrate the HPV serology standard to World Health Organization (WHO) international standards (IS)s for HPV 16 (IS16) and HPV 18 (IS18), establishing it as a secondary standard for these types with unitages directly traceable to the ISs. The candidate was produced using anti-serum from recipients of the nonavalent HPV vaccine. Nine laboratories from seven countries participated in the study using pseudovirion-based neutralization assays (PBNAs) and Ab-binding assays to detect HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 neutralizing and IgG antibodies, respectively, to test a panel of coded samples across independent assays. The panel consisted of the candidate standard, seronegative samples, and plasma references derived from recipients of a bivalent vaccine, IS16, and IS18. The study showed that the between-laboratory variability of results for neutralizing antibodies or Ab-binding levels is reduced when values are expressed relative to those of the IS16, IS18, or candidate standard, allowing greater comparability between laboratories. Based on these findings, unitages were assigned to the calibrated HPV serology secondary standard: 904 IU/mL (HPV 16 PBNA), 365 IU/mL (HPV 18 PBNA), 508 IU/mL (HPV 16 Ab-binding), and 270 IU/mL (HPV 18 Ab-binding), and the calibrated candidate standard should be utilized by the scientific community to minimize the use of the WHO international standards and preserve its stock. The HPV serology secondary standard is available to the scientific community to help harmonize results between laboratories.IMPORTANCEA human papillomavirus (HPV) serology secondary standard derived from serum donated by recipients of the nonavalent HPV vaccine was calibrated in a multicenter international collaborative study using World Health Organization international standards for antibodies to HPV type 16 and HPV type 18. The secondary standard was assigned unitages in globally recognized International Units (IU)/mL and was demonstrated to harmonize results for neutralizing antibody and antibody-binding assays to detect HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 neutralizing and IgG antibodies, respectively, across laboratories. The HPV serology secondary standard is publicly available to HPV laboratories for calibrating assays and reporting antibody results in IU/mL. It is a critical resource for assay standardization, enabling the comparison of results across HPV vaccine immunogenicity studies and HPV serosurveillance studies. This fills an important standardization gap in HPV antibody reporting.

BACKGROUND:Initially approved as a three-dose regimen, evolving evidence has supported the efficacy of reduced-dose schedules. Single-dose HPV vaccine data among males remain scarce. This study assesses the persistence of antibodies against HPV16/18 following a single HPV vaccine dose and the immune response to a subsequent delayed dose administered at least three years later in girls and boys. METHODS:This single-group descriptive study involved youth from the Quebec City area, Canada, who received a single dose of 4vHPV (girls) or 9vHPV (boys) as part of the public school-based vaccination program. A blood sample was collected 3-10 years post-initial vaccination. Girls and boys then received one 9vHPV or 2vHPV booster dose, respectively, and had a second blood draw one month later. Serological assays were conducted using M9ELISA. RESULTS:Four years after the initial 9vHPV dose, among 141 boys aged 12 to 14 years 96.5 % and 97.9 % had detectable antibodies against HPV16 and HPV18, respectively. Among girls aged 13 to 24 years vaccinated 3-10 years prior with one 4vHPV dose, 95.0 % (HPV16) and 93.3 % (HPV18) had detectable antibodies. One-month post-second dose administration, all participants were seropositive for HPV16/18, with significant increases in geometric mean concentrations (GMCs). CONCLUSION:A single dose induces a strong and lasting immune response in girls (4vHPV) and boys (9vHPV), with a significant antibody anamnestic boost following a second dose administered several years later. These findings indicate the potential for a single-dose or a delayed booster strategy in both sexes, and support studies showing effectiveness of single-dose schedules. TRIAL REGISTRATION:The study is registered with ClinicalTrials.gov (NCT03431246).

Human papillomavirus (HPV)-associated cancers are vaccine preventable. In 2016, the previously recommended three-dose HPV vaccination series was changed to a two-dose series and nine-valent HPV vaccine (9vHPV) became the only HPV vaccine available in the United States. Data on longer-term duration of antibodies following a 9vHPV two-dose series are limited. We evaluated the immunogenicity and duration of antibodies up to three years after vaccination with a two-dose series of 9vHPV in a cohort of Alaska Native children. We enrolled Alaska Native children aged 9–14 years who received 9vHPV in Anchorage, Alaska during 2017–2018. We collected sera at six months after dose one and at one month, one year, and three years after dose two to measure type-specific immunoglobulin G (IgG) concentrations for the 9vHPV types (HPV6/11/16/18/31/33/45/52/58). Aggregate type-specific IgG concentrations were reported as geometric mean concentrations (GMC). A total of 227 children completed the two-dose series of 9vHPV and provided ≥ 1 blood sample. The median age at enrollment was 11.0 years (range: 9.0–14.6) and was similar between males and females (p = 0.11). At one month after dose two, all 197 participants with available serum were seropositive for all 9vHPV types. Among 145 participants who had a specimen available at three years after dose two, 134 (92

BACKGROUND:Antibody persistence in girls (age 9-11 years) receiving two quadrivalent vaccine (4vHPV) doses and impact of an additional dose five years post-primary vaccination were assessed. METHODS:Girls vaccinated with two 4vHPV (Gardasil) doses (n = 496) were randomized to one- (2 + 1) or no-additional-dose groups five years post-first dose. Geometric mean concentrations (GMCs) for HPV types 6/11/16/18 were measured using M9ELISA at 5, 7.5, and 10 years post-primary vaccination. RESULTS:Antibodies to 4vHPV-targeted types persisted in all participants at each time point in both study arms. Compared to the 2-dose group that had stable antibody levels up to 10 years, GMCs were higher in the 2 + 1 group at 7.5 and 10 years post-primary vaccination (p < .0001). CONCLUSIONS:Two doses of 4vHPV administered at ages 9-11 confers stable antibody levels up to 10 years post-vaccination that can be enhanced with an additional dose given several years later, suggesting the presence of immune memory.

Background: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine -preventable. Studies suggest long-term persistence of vaccine -induced antibodies. However, data are limited among Alaska Native people. Methods: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3 -dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post -vaccination to evaluate trends in type -specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/ 18). Results: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints postvaccination. For all 4vHPV types, antibody levels peaked by 1 month post -vaccination and gradually declined in subsequent years. At 5 years post -vaccination, antibody levels were higher among children who received 4vHPV at a younger age. Conclusions: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post -vaccination.

BackgroundWithin the United States, a 9-valent human papillomavirus (9vHPV) vaccine (HPV-6/11/16/18/31/33/45/52/58) is recommended as a two-dose series among individuals 9 to 14 years of age and a three-dose series among those 15 to 26 years of age. Data comparing two versus three doses of 9vHPV vaccine among individuals 15 to 26 years of age are limited.MethodsWe report on an ongoing, single-blinded, randomized noninferiority trial of the 9vHPV vaccine among individuals 15 to 26 years of age in the United States. Participants were randomly assigned to a two-dose (0 and 6 months) or three-dose (0, 2, and 6 months) schedule. Blood draws to assess antibody titers were planned before the first vaccination and at 1 and 6 months after the final vaccination. The primary outcome was the rate of seroconversion at 1 month after final vaccination. The secondary outcome was the two-dose versus three-dose ratio of antibody geometric mean titers (GMTs) for each of the 9vHPV genotypes at 1 and 6 months after final vaccination. This interim analysis reports results of female participants at 1 month after final vaccination.ResultsOf 860 participants screened, 438 were enrolled and randomly assigned to the two-dose (n=217) or three-dose (n=221) group. At 1 month after the final vaccine dose, the seroconversion rate for each of the nine HPV genotypes in the vaccine was 100% among participants in the two-dose group and 99% in the three-dose group. The point estimates of the two-dose versus three-dose ratios of antibody GMTs for eight of the nine HPV genotypes were above unity; the ratio for HPV-45 was 0.86 (95% confidence interval [CI], 0.66 to 1.13). This was also the smallest value for the lower bound of the 95% CI for all nine ratios (ratios above 1 favor the two-dose schedule). No serious adverse events were observed.ConclusionsIn this unplanned interim analysis of U.S. female participants 15 to 26 years of age, two doses of 9vHPV vaccine appear to elicit responses similar to three doses at 1 month postvaccination. We await final results at 6 months following the last vaccine dose. (ClinicalTrials.gov number, NCT03943875.) This noninferiority trial examined two versus three doses of 9-valent human papillomavirus (9vHPV) vaccine in individuals 15 to 26 years of age in the United States. In an unplanned interim analysis of female participants, two doses of 9vHPV vaccine appeared to elicit similar rates of seroconversion and antibody titers for each of the nine HPV genotypes to three doses at 1 month postvaccination.

Abstract Introduction Human papillomavirus (HPV) surveillance is lacking in Puerto Rico (PR). We aim to estimate the seroprevalence of the HPV types included in the nonavalent vaccine (9vHPV) in women and explore associations. Methodology A population-based cross-sectional study of socio-demographic, clinical [including, sexually transmitted infections (STIs)], and behavioral characteristics of sexually active women (16-64 years) was conducted in PR from 2010-2013. Blood samples from 524/566 (92.6%) HPV unvaccinated women were included in this sub- analysis. Antibody responses to 9vHPV types (HPV-6/11/16/18/31/33/45/52/58) were analyzed using M9ELISA by the U.S. Centers for Disease Control and Prevention (CDC). A self-collected cervical and anal sample from all 524 women were also tested using L1 consensus primer (MY09/MY11) PCR followed by dot hybridization to detect 40 HPV types. Statistical analyses included Pearson’s chi-square and logistic regression models. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were reported. Results The mean age of participants was 42.4 years ± 0.6 standard deviations (SD), 52.5% were married/cohabited, and 9.7% were uninsured. About half (51.3%) had between 3-9 lifetime sexual partners, 15.9% had history of STIs, and 40.3% had a current anogenital HPV infection. Overall, 65.8% were seropositive to at least one of the 9vHPV types (1.0% to all 9vHPV types), 59.9% to any of the seven oncogenic types (HPV-16/18/31/33/45/52/58) and 49.1% to any of the quadrivalent vaccine (4vHPV) types. The seroprevalence for specific HPV types ranged between 10.7%-28.1% [HPV-33 (10.7%), 11 (11.6%), 45 (11.8%), 58 (15.8%), 18 (18.7%), 31 (25.0%), 6 (26.2%), 52 (26.9%), and 16 (28.1%)]. In bivariate analysis, significant associations between 9vHPV types were observed with marital status, age at sexual debut, lifetime sexual partners, anal sex, history of STIs and anogenital HPV infection (p<0.05). In the multivariate model, divorced/separated/widowed women (aOR: 2.2, 95%CI: 1.2-4.3) had higher odds of seropositivity to any of the 9vHPV types than single women. Women with 3-9 (aOR: 2.4, 95%CI, 1.5-3.8) and with >10 (aOR: 3.1, 95%CI, 1.6-5.8) lifetime sexual partners had higher odds of seropositivity than women with 1-2 partners. Women with a history of STIs (aOR: 2.1, 95%CI, 1.1-4.0) and with an anogenital HPV infection (aOR: 1.9, 95%CI, 1.2-2.9) had higher odds of HPV seropositivity than their counterparts. In this model, no differences were observed by age, education, healthcare coverage, age at sexual debut or anal sex. Conclusion Before implementation of the HPV nonavalent vaccine, the seroprevalence of at least one of the 9vHPV types among women in PR was high (65.8%). However, less than 1% of women were seropositive for all nine HPV types, indicating this population would benefit from HPV vaccine implementation. Acknowledgements Study funded by the National Institute of Allergy and Infectious Diseases Grant (Grant #1SC2AI090922-01) of the National Institutes of Health. Citation Format: Angeline Cruz, Jeslie M. Ramos-Cartagena, Gitika Panicker, Elizabeth Unger, Ana P Ortiz. The seroprevalence of nine human papillomavirus types included in the nonavalent vaccine in unvaccinated women living in Puerto Rico [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A112.

BACKGROUND:With accumulating evidence of single-dose human papillomavirus (HPV) vaccine efficacy in young women, we conducted a community vaccine effectiveness study comparing HPV single-dose and 2-dose regimens (0 and 6 months) of a bivalent HPV vaccine among grade 8 schoolgirls (aged 13-14 years) in Thailand. METHODS:In 2018, eligible grade 8 schoolgirls in Udon Thani (single dose) and Buri Ram (2 doses) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey for measuring baseline HPV prevalence was conducted in grade 10 (n = 2600) and grade 12 unvaccinated schoolgirls (n = 2000) in each province. HPV infection was assessed in first-void urine samples, tested by DNA polymerase chain reaction on the cobas 4800 system (Roche Molecular Diagnostics, Pleasanton, CA). All samples positive on the cobas system and an equal number of negative samples were also tested by Anyplex II HPV28 Detection (Seegene, Seoul, South Korea). The surveys were repeated in 2020 and 2022, when vaccinated grade 8 schoolgirls reached grade 10, and then subsequently grade 12, respectively. Vaccine effectiveness was estimated by comparing the weighted prevalence of HPV-16 or HPV-18 between grade-matched unvaccinated schoolgirls on the baseline survey (2018) and vaccinated schoolgirls in the year-2 (2020) and year-4 (2022) surveys. Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the noncontemporaneous comparison. RESULTS:The prevalence of HPV-16 and HPV-18 on the baseline survey among unvaccinated grade 10/grade 12 schoolgirls was 2.90% (95% confidence interval [CI] = 2.54% to 3.31%)/3.98% (95% CI = 3.52% to 4.49%) for Udon Thani and 3.87% (95% CI = 3.46% to 4.34%)/6.13% (95% CI = 5.56% to 6.75%) for Buri Ram. On the year-2 survey, the prevalence among vaccinated grade 10 schoolgirls was 0.57% (95% CI = 0.42% to 0.77%) for Udon Thani and 0.31% (95% CI = 0.21% to 0.47%) for Buri Ram. The 2-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 80.4% (95% CI = 73.9% to 86.9%), and for the 2-dose regimen at 91.9% (95% CI = 88.5% to 95.4%). On the year-4 survey, the prevalence among vaccinated grade 12 schoolgirls was 0.37% (95% CI = 0.25% to 0.56%) for Udon Thani and 0.28% (95% CI = 0.18% to 0.45%) for Buri Ram. Four-year postvaccination crude vaccine effectiveness for the single-dose regimen was estimated at 90.6% (95% CI = 86.6% to 94.6%) and for the 2-dose regimen was estimated at 95.4% (95% CI = 93.2% to 97.6%). All adjustment methods minimally affected vaccine effectiveness for the single-dose and 2-dose regimens. At 4 years after vaccination, the difference in crude vaccine effectiveness between the single-dose and 2-dose regimens was ‒4.79% (95% CI = ‒9.32% to ‒0.25%), meeting the study's noninferiority criteria. CONCLUSIONS:Our study demonstrated that both single-dose and 2-dose HPV vaccination significantly decreased HPV-16/18 point prevalence 2 years and 4 years after vaccination. Crude vaccine effectiveness at 4 years after vaccination was greater than 90% for both the single-dose and 2-dose regimens; the single-dose regimen was not inferior to the 2-dose regimen. These data show that a single dose of HPV vaccine provides high levels of protection when administered to schoolgirls younger than 15 years of age.

Previously established World Health Organization (WHO) International Standards (IS) for anti-HPV16 and HPV18 antibodies are used to harmonize results across human papillomavirus (HPV) serology assays. Here, we present an international collaborative study to establish ISs for antibodies against HPV6 (NIBSC code 19/298), HPV11 (20/174), HPV31 (20/176), HPV33 (19/290), HPV45 (20/178), HPV52 (19/296) and HPV58 (19/300). The candidate standards were prepared using sera from naturally infected individuals. Each candidate was shown to be monospecific for reactivity against its indicated HPV type except for the HPV11 candidate, which was also reactive against other types. Expression of antibody levels relative to the relevant candidate IS reduced inter-laboratory variation allowing greater comparability between laboratories. Based on these results, the WHO Expert Committee on Biological Standardization established each of the 7 candidates as the 1st IS for antiserum to its indicated HPV type for use in the standardization of HPV pseudovirion-based neutralization and antibody-binding assays.

Background: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women.Methods: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women.Results: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination.Conclusion: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first‐void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first‐void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type‐specific antibody responses to the 9vHPV types were analyzed in 174 first‐void urine and 172 serum samples using a virus‐like particle‐based IgG multiplex enzyme‐linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%–100% of first‐void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%–100% of first‐void urine and 98%–100% of serum samples had HPV‐specific antibody concentrations. Results show significant Spearman rank correlations between type‐specific HPV‐antibody concentrations for paired first‐void urine and serum at all time points. This study confirms the potential feasibility of utilizing first‐void urine as a noninvasive immunological sample within HPV vaccine trials.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

Background: With accumulating evidence single dose (SD) HPV vaccine efficacy in young women, we are conducting a community vaccine effectiveness (VE) study comparing HPV SD and 2-dose (2D) regimens (0, 6 months) of a bivalent HPV vaccine, in Thailand among 13-14 year-old Grade 8 schoolgirls.Methods: In 2018, eligible Grade 8 schoolgirls in Udon Thani (SD) and Buriram (2D) provinces were offered HPV vaccine per assigned dose regimen. Concurrently, a cross-sectional survey (CSS) of HPV prevalence was conducted in Grade 10 schoolgirls (N=2,600 in each province). HPV infection was assessed in first-void urine samples, tested by DNA PCR Cobas 4800. All Cobas positive samples and an equal number of negative samples were also tested by Anyplex II HPV 28. In 2020, when vaccinated Grade 8 schoolgirls reached Grade 10, the CSS was repeated. VE was estimated by comparing weighted prevalence of HPV 16 or 18 between baseline CSS (2018) and vaccinated schoolgirls in Year-2 CSS (2020). Adjustment methods were used in the analysis to account for potential differences in sexual behavior due to the non-contemporaneous comparison.Findings: Prevalence of HPV16 or 18 in baseline CSS was 2.92% (95% CI 2.57-3.33) and 3.40% (95% CI 3.04-3.81) for Udon Thani and Buriram, respectively. In Year-2 CSS, the prevalence among vaccinated schoolgirls was 0.50% (95% CI 0.34-0.71) for Udon Thani and 0.22% (95% CI 0.14-0.35) for Buriram. Estimated unadjusted VE for SD was 83.0% (95% CI: 76.4-89.6), and for 2D was 93.6% (95% CI: 90.5-96.8). All adjustment methods minimally impacted VE estimates for SD (80%~83%) and 2D (91%~93%).Interpretation: Two years post-vaccination with SD HPV vaccination, estimated VE against HPV 16 and 18 infection was high among teenage schoolgirls in Thailand.Trial Registration Details: The study is registered at clinicaltrials.gov with the identifier NCT03747770.Funding Information: This study was funded by the Bill & Melinda Gates Foundation.Declaration of Interests: All authors declare having no conflict of interest.Ethics Approval Statement: The study protocol was approved by the Thailand Ministry of Public Health (MoPH) Ethical Committee (EC), the International Vaccine Institute Institutional Review Board, and the Chulalongkorn University EC.

Journal of Medical VirologyVolume 95, Issue 10 e29206 COVERFree Access Cover Image, Volume 95, Number 10, October 2023 Laura Téblick, Corresponding Author Laura Téblick [email protected] orcid.org/0000-0002-7484-0956 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium Correspondence Laura Téblick, Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, B-2000 Antwerp, Belgium. Email: [email protected]Search for more papers by this authorJade Pattyn, Jade Pattyn orcid.org/0000-0002-4538-9027 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorSeverien Van Keer, Severien Van Keer Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorAnnemie De Smet, Annemie De Smet Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorIlse De Coster, Ilse De Coster Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorWiebren A. A. Tjalma, Wiebren A. A. Tjalma Multidisciplinary Breast Clinic, Gynecological Oncology Unit, Department of Obstetrics and Gynecology. Antwerp University Hospital (UZA) (Belgium), Molecular Imaging, Pathology, Radiotherapy, and Oncology (MIPRO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorIra Rajbhandari, Ira Rajbhandari Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorGitika Panicker, Gitika Panicker Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorElizabeth R. Unger, Elizabeth R. Unger orcid.org/0000-0002-2925-5635 Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorAlex Vorsters, Alex Vorsters Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this author Laura Téblick, Corresponding Author Laura Téblick [email protected] orcid.org/0000-0002-7484-0956 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium Correspondence Laura Téblick, Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, B-2000 Antwerp, Belgium. Email: [email protected]Search for more papers by this authorJade Pattyn, Jade Pattyn orcid.org/0000-0002-4538-9027 Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorSeverien Van Keer, Severien Van Keer Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorAnnemie De Smet, Annemie De Smet Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorIlse De Coster, Ilse De Coster Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorWiebren A. A. Tjalma, Wiebren A. A. Tjalma Multidisciplinary Breast Clinic, Gynecological Oncology Unit, Department of Obstetrics and Gynecology. Antwerp University Hospital (UZA) (Belgium), Molecular Imaging, Pathology, Radiotherapy, and Oncology (MIPRO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this authorIra Rajbhandari, Ira Rajbhandari Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorGitika Panicker, Gitika Panicker Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorElizabeth R. Unger, Elizabeth R. Unger orcid.org/0000-0002-2925-5635 Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USASearch for more papers by this authorAlex Vorsters, Alex Vorsters Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, BelgiumSearch for more papers by this author First published: 25 October 2023 https://doi.org/10.1002/jmv.29206AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Front Cover Caption: The cover image is based on the Research Article Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study by Laura Téblick et al., https://doi.org/10.1002/jmv.29133. Volume95, Issue10October 2023e29206 RelatedInformation

Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch® and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine.

High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96–11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.

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.