Nonavalent Vaccine Research Articles

Prospectives of developing therapeutic HPV vaccines

Human papillomavirus (HPV) represents one of the most serious global public health problems. Malignant female and male diseases mainly result from persistent HPV infection. Cancer belongs to a high mortality rate disease. It has been established that HPV infection causes about 70% vaginal cancer, 50% male genital cancer, 90% anal cancer and 60% head-and-neck cancer. Annually, a large number of people develop various HPV-caused cancer types, dominated by cervical cancer, one of the most common and aggressive types of cancer that threatens health holding the fourth place among most female common cancer worldwide. According to the World Health Organization (WHO), in 2020, about 600 cases of cervical cancer are recorded daily in different countries. Emergence of cervical cancer is closely related to factors such as long-term (persistent) HPV infection and somatic mutations of the host genome. Although HPV infection can be detected and cured early with highly effective screening methods and surgical procedures, the carcinogenic risk of HPV related diseases constantly increases, which elimination faces certain difficulties, especially in low- and mid-developed countries. The most acceptable solution to this is development and implementation of therapeutic vaccines for prevention and treatment of HPV related diseases. Three licensed HPV vaccines based on L1 type virus-like particles (L1-VLPs) technology are available globally: bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent (HPV-9) vaccines. These vaccines demonstrated effectiveness in reducing HPV-related cervical cancer rate by up to 90% worldwide. However, the therapeutic effect of these vaccines on persistent HPV infection and lesions has not been observed. Therapeutic HPV vaccines candidates targeted Ye6/Ye7 cancer proteins activate cellular immunity that eliminates existing HPV infection. Here we review types, mechanisms of action and clinical effects of therapeutic HPV vaccines, as well as current and future developments in the field for prevention and treatment of HPV related diseases.

HPV Vaccines

Human papillomavirus (HPV) is a double-stranded DNA virus and a source of infection that primarily affects the skin and mucous membranes. It can be transmitted through sexual contact and contaminated surfaces. There are over 200 genotypes of HPV, approximately 40 of which infect the anogenital region. High-risk HPV types, such as HPV-16 and HPV-18, can lead to the development of various cancers, particularly cervical cancer. Factors that increase the risk of transmission include having multiple sexual partners, early initiation of sexual activity, and having an uncircumcised male partner. Low socioeconomic status, poor nutrition, immunosuppression, and co-infections with HIV, genital herpes, or chlamydia can result in persistent and severe HPV infection. Three types of vaccines have been developed against HPV: bivalent, quadrivalent, and nonavalent vaccines. The bivalent vaccine provides protection against HPV-16 and HPV-18; the quadrivalent vaccine is effective against HPV-16, HPV-18, as well as HPV-6 and HPV-11. The nonavalent vaccine offers the broadest protection, covering nine different types of HPV. All vaccines are approved for males and females aged 9 and older. Vaccination before the onset of sexual activity significantly increases protection against cervical cancer.

Prevalence and distribution of human papillomavirus genotypes in women with abnormal cervical cytology in Ethiopia: a systematic review and meta-analysis.

Cervical cancer is the 4th most common cancer in women globally. Determining the prevalence of the high-risk human papillomavirus (HR-HPV) and low-risk (LR-HPV) genotypes and the distribution in abnormal cervical cytology will be essential in a future population-based cervical cancer prevention program. Primary studies with women with abnormal cervical cytology were systematically searched for in Medline, CINHAL, Google Scholar, African Journal Online, and the University of Antwerp repository from 19-30 May 2023. A weighted inverse-variance random effects model was used. Variations across the studies were checked using a forest plot, I2 statistics, and Egger's test. Group analysis was performed for evidence of heterogeneity. The pooled prevalence of human papillomavirus (HPV) genotypes with abnormal cervical cytology of a precancerous cervical lesion was 38.74% (95% CI: 27.56-49.93). The leading pooled prevalence estimates by subgroup analysis were 18% (95% CI: 13-26), 14% (95% CI: 111-16), and 66% (51-79) for women with retroviral infection (RVI), DNA genotyping with amplification, and central parts of Ethiopia respectively. There were 25 HPV variants identified by genotyping techniques with the five most prevalent HPV genotypes being HPV-16 and HPV-18 coexisting at 54%; HPV-16 alone at 29%; HPV-51 at 16%; HPV-52 at 13%; and HPV-31 and HPV-33 each contributing approximately 12%. The pooled prevalence of HPV genotypes was higher than in other countries. HPV-51, HPV-52, HPV-31, and HPV-33 are the most prevalent genotypes. Hence, the nonavalent vaccine type would be the one that includes all the most prevalent HPV genotypes, but HPV-51in Ethiopia. Additional data on similar DNA test techniques for comparisons with precancerous lesions and invasive cancer are needed. Cervical cancer prevention and control programs in Ethiopia should be aligned with the most prevalent genotypes. https://www.crd.york.ac.uk/prospero/, identifier CRD42023428955.

Cost-effectiveness of nonavalent vs bivalent HPV vaccine in Polish setting.

Human papillomavirus (HPV) is a prevalent sexually transmitted infection with significant implications for public health. In Poland, a nationwide vaccination program offers a choice between the 9-valent (9v) and 2-valent (2v) HPV vaccines. We aimed to assess the cost-effectiveness of the 9v vs 2v vaccine from the public payer perspective in Poland. A cost-effectiveness analysis was conducted to compare the public health and economic benefits of using 9v vs 2v vaccine in Poland over 100-year horizon using a previously published deterministic dynamic transmission model. A target population of girls and boys aged 12-13 years was considered. The model was populated with local epidemiological inputs, utilities, and costs, including vaccine and administration costs, as well as costs related to medical procedures for HPV-related diseases. The 9v vaccine reduced the prevalence of HPV infections and HPV-related diseases substantially more than 2v vaccine when both are compared to no vaccination strategy. The total discounted cost savings of using the 9v vaccine instead of 2v, excluding the vaccine costs, amounted to EUR 66 million. The incremental cost-effectiveness ratio amounted to 8094 EUR per quality-adjusted life year, much below the official cost-effectiveness threshold in Poland set up at the three times the annual gross domestic product per capita. 9v cost-effectiveness ratio remained unchanged when shorter time-horizons of 20, 40, 60, or 80 years were considered. Using 9v HPV vaccine in Poland is highly cost-effective compared to the 2v vaccine.

Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study

ObjectiveTo assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent...

Abstract A112: The seroprevalence of nine human papillomavirus types included in the nonavalent vaccine in unvaccinated women living in Puerto Rico

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.

Population-based age- and type-specific prevalence of human papillomavirus among non-vaccinated women aged 30 years and above in Germany

BackgroundA persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above.MethodsThe MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, ‘moderate’ risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types.Results2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% ’moderate’ risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30–34 years (HR 9.8%, ‘moderate’ risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection.ConclusionThe overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination.

Human papillomavirus type-specific distribution in cervical intraepithelial neoplasia and cancer in The Gambia prior to HPV immunization programme: a baseline for monitoring the quadrivalent vaccine

BackgroundCervical cancer is the leading cause of cancer deaths in Gambian women. Current estimates indicate that 286 women are annually diagnosed with cervical cancer with a fatality rate of 70%. In an attempt to address this, in 2019 the quadrivalent HPV vaccine was incorporated into the Gambia’s Expanded Programme on Immunisation. The study aims to retrospectively assess the prevalence and distribution of high-risk HPV genotype in archived, formalin fixed paraffin embedded cervical biopsy tissues diagnosed with cervical cancer in the Gambia from year 2013–2022.MethodA total of 223 samples with histologically diagnosis of cervical cancer with adequate tissues were sectioned and deparaffinised, followed by HPV DNA extraction and the detection of HR-HPV by real-time multiplex PCR. The human β-globin gene was amplified in 119 samples, which were subsequently tested for HPV DNA.ResultsHPV was prevalent in 87.4% (104 of 119) cervical cancer cases, 12.6% (15/119) samples tested negative. Amongst cervical cancer cases, HPV 16 genotype was the most frequent type accounting for 53.8% (56 /104), followed by other HR-HPV genotypes 17.3% (18/104), and HPV genotype 18 was 15.4% (16/104). Furthermore, multiple HPV infections involving HPV 16 and /or 18 was detected in 14 cases as follows: HPV genotypes 16 and 18 (3.8%, 4 /104), HPV 16 and other HR-HPV (6.7%, 8/104), and HPV 18 and other HR-HPV (1.9%, 2/104). A significant association between age and diagnosis with cervical cancer (p = 0.02), and HPV genotype 16 (p = 0.04) was observed.ConclusionThere was no difference in the distribution of HPV 16 and 18 genotypes in cervical cancer cases in The Gambia in comparison with the global distribution. However, the high prevalence of cervical cancer cases with other HR-HPV, and combined infections of HPV 16 with other HR-HPV genotypes seen in this study, clearly shows that the nonavalent HPV vaccine could be more beneficial for The Gambia. This study provides The Gambia with a baseline data to use in policy decisions regarding future evaluation of the quadrivalent HPV vaccine in the country.

Trends in human papillomavirus infection and genotype distribution among males in Chongqing, China (2017-2022): an observational study.

This study aimed to investigate Human papillomavirus (HPV) infection and genotyping in men from Chongqing and analyze age-related trends to provide insights for HPV prevention and vaccination plans tailored for men in Chongqing, China. This study is an observational study. We investigated male patients who underwent HPV screening at two hospitals in Chongqing from 2017 to 2022, totaling 4,381 cases, aged 18 to 85. HPV genotyping was conducted using the Hybribio Rapid GenoArray kit. Among the 4,381 men, the overall HPV prevalence was 14.9%, peaking at 19.3% in 2022. Single HPV infection was 11.5%, and multiple infection was 3.4%. The most prevalent genotypes were HPV-52, HPV-16, and HPV-58. Single high-risk HPV infection peaked in the 36-45 age group, while multiple high-risk HPV infection decreased with age (P-trend < 0.01). Prevalence in the ≤ 25 age group was 3.7%. Single low-risk HPV infection also decreased with age (P-trend = 0.03). Genotypes covered by the nonavalent vaccine had the highest prevalence, increasing with age. Co-infection of HPV-16 with HPV-52 and HPV-58 was common. Single HPV infections were prevalent in cases of urethritis (30.8%), anogenital warts (36.4%), and genital warts (26.3%), while multiple HPV infections were significant in anogenital warts (18.2%). Single HPV infection was predominant in Chongqing, with HPV-52, HPV-16, HPV-58, HPV-53, and HPV-39 being the most prevalent genotypes. The prevalence of genotypes covered by the nonavalent vaccine increased with age. This study offers valuable insights for developing male-specific HPV prevention strategies in Chongqing.

HPV infection patterns and viral load distribution: implication on cervical cancer prevention in Western Kenya.

Human papillomavirus (HPV) coinfection remains common globally. However, its clinical significance compared to mono-infection remains controversial. Further, the epidemiology of HPV genotype combination in coinfection is not well studied in Kenya. . Between June and August 2023, a cross-sectional facility-based survey enrolled 434 women aged 16-68 years using purposive sampling strategy. Structured questionnaire was obtained from each woman regarding demographic and sexual behavior characteristics. Cervical specimen was collected from each participant and analyzed using RIATOL assay to determine HPV genotypes and viral load. Overall, HPV 52 was the most frequently detected HPV strain. The mean HPV viral load was elevated among coinfected women than those with mono-infection but there was no evidence to support differences in viral load in the two groups (P = 0.113). Mono-infection was common (58.52%). HPV 16 was noted to have a near equal presence both in mono-infection and coinfection (52.17% and 47. 83%), respectively. HPV 33 (alpha 9) and 45 (alpha 7) had the greatest preference for each other compared to all other HPV interactions. HPV 52 is the most prevalent HPV in the population supporting the need for the nonavalent HPV vaccine. Mono-infection with HPV 16 remains common corroborating the relevance of bivalent vaccine in resource limited setting where nonavalent vaccines may be unavailable. The frequent coinfection preference of HPV 33 and 45 (alpha 9 and alpha 7, respectively) pauses the need for further concurrent characterization. HPV vaccination and education on safe sexual behaviors is key in reducing HPV coinfection.

The Clinical Effectiveness of Single-Dose Human Papillomavirus Vaccination.

The human papillomavirus (HPV) vaccine was initially approved for a three-dose regimen. Due to resource limitations, budget constraints, low acceptance, and poor adherence, global vaccination coverage is only 15%. A single-dose regimen could simplify logistics, reduce costs, and improve accessibility. However, its clinical effectiveness remains debatable. This review systematically searched PubMed, Embase, and Cochrane Library, including 42 clinical studies, to assess the effectiveness of a single-dose HPV vaccination for preventing HPV infections, cervical abnormalities, and genital warts. We summarized the effectiveness of bivalent, quadrivalent, and nonavalent vaccines across different age groups and buffer periods, and analyzed the factors contributing to the inconsistency of results. The review also provides insights into designing robust future research to inform single-dose HPV vaccination policies and guidelines, highlighting the need for further research to refine vaccination strategies.

Prevalence of human papillomaviruses in self-collected samples among women attending antenatal care in Ethiopia: a cross-sectional study.

Cervical cancer is the second most commonly diagnosed cancer in women in Ethiopia. However, data are limited on the prevalence of human papillomavirus (HPV) genotypes. Self-sampled vaginal lavages were obtained consecutively from 783 women attending 7 health facilities across Ethiopia. Genotype prevalence was assessed by Multiplex-Papillomavirus-Genotyping which detects and individually identifies 51 genotypes and 3 subtypes. Genotype-specific prevalence was described and associations with known risk factors were analysed. The overall HPV prevalence (age range 18-45) was 33.1% (95% confidence interval (CI) 29.8-36.4). The prevalence of HPV was different in the rural and urban population with 17.6% (95%CI 11.6-23.7) and 36.8% (95%CI 33.1-40.6) (p < 0.001 chi-square test), respectively. The most common high-risk types were HPV 16 (6.6%), followed by HPV 52 (4.3%), 51 and 39 (both 2.9%). Urban women compared to rural women had a higher risk of being HPV positive (odds ratio 2.36 (95% CI 1.47-3.79; p < 0.001). Age at sexual debut ≤15 years and polygamous husband (in urban women) also increased the risk of being HPV positive nearly two-fold. The high prevalence of hr-HPV in Ethiopian women in the reproductive age group shows the need for screening programs. The nonavalent HPV vaccine covers the most prevalent hr-HPV genotypes as found in this study and can therefore be used effectively. Since antenatal care is the best-utilised health service, implementing self-sampled vaginal lavage could be an opportunity for screening in this age group. Screening algorithms and triage still need to be defined to avoid over-treatment in these women.

Pap Cytology and Human Papillomavirus (HPV) Genotypes in Western Romania: A Retrospective Analysis.

Background and objective Vigorous proactive measures are needed to combat cervical cancer, linked to the human papillomavirus (HPV). HPV genotyping aids in identifying high-risk strains, enabling targeted screening and risk assessment. This informs treatment decisions, reducing cervical cancer cases. In light of this, we conducted aretrospective analysis of Pap cytology and HPV genotypes to assess western Romania's new screening program. Understanding HPV prevalence, genotype correlations, and risk factors will help refine risk stratification models and enhance public health strategies. Methodology This retrospective studyanalyzed Pap smears from 195 patients with a mean age of 40 years [standard deviation (SD): 12 years], with a peak of incidence between 25 and 30 years. The patient cohort, with equal representationfrom urban and rural areas, comprised sexually active women of reproductive age presenting to the Gynaecology Ambulatory of the Municipal Emergency Clinical Hospital Timișoara over two years. Patients not sexually active and those in menopause were excluded. HPV genotyping was done on 67 patients. Data were analyzed using JASP, employing descriptive statistics, frequency tables, contingency tables, chi-squared test, odds ratio, and Fisher's exact test. Results Among 195 patients undergoing Pap smear tests, the most prevalent finding was negative (77.95%), indicating no abnormal cells detected. A smaller proportion of patients exhibited low-grade squamous intraepithelial lesions (LSIL, 11.28%) or atypical squamous cells of undetermined significance (ASC-US, 8.72%) findings. High-grade lesions (HSIL, ASC-H) were rare. For cytology grading, Category II (CII) was the most prevalent (75.90%), followed by Category III (CIII, 24.10%). HPV genotyping was performed on a subset of patients (n=67). Among them, Type 16 was the most frequent (28.36%), followed by Other high-risk types(20.89%), Type 16 (28.35%), and Type 18 (13.43%). HPV testing was not performed for 65.64% of the patients. Overall, the study suggests that a significant majority of the patients had normal Pap smears. However, a small proportion did have abnormal findings, including HPV infection. These findings highlight the importance of Pap smear screening for early detection of cervical abnormalities. Conclusions Our study from western Romania highlights the importance of HPV testing and Pap cytology in cervical cancer prevention. HPV testing is a potent tool for identifying high-risk women, and when combined with Pap cytology, it provides a more comprehensive screening strategy. Our research also revealed a diverse HPV genotype distribution, suggesting the need for broader-spectrum vaccines like the nonavalent vaccine. Despite our study's limitations, our findings underscore the need for including HPV testing in national screening guidelines. Future research should focus on larger studies and the cost-effectiveness of broader-spectrum vaccines. Implementing policies based onthese findings could lead to more effective cervical cancer prevention in western Romania.

Immunogenicity of a Rotavirus VP8* Multivalent Subunit Vaccine in Mice.

Rotavirus remains a significant public health threat, especially in low-income countries, where it is the leading cause of severe acute childhood gastroenteritis, contributing to over 128,500 deaths annually. Although the introduction of the Rotarix and RotaTeq vaccines in 2006 marked a milestone in reducing mortality rates, approximately 83,158 preventable deaths persisted, showing ongoing challenges in vaccine accessibility and effectiveness. To address these issues, a novel subcutaneous vaccine formulation targeting multiple rotavirus genotypes has been developed. This vaccine consists of nine VP8* proteins from nine distinct rotavirus genotypes and sub-genotypes (P[4], P[6], P[8]LI, P[8]LIII, P[8]LIV, P[9], P[11], P[14], and P[25]) expressed in E. coli. Two groups of mice were immunized either with a single immunogen, the VP8* from the rotavirus Wa strain (P[8]LI), or with the nonavalent formulation. Preliminary results from mouse immunization studies showed promising outcomes, eliciting antibody responses against six of the nine immunogens. Notably, significantly higher antibody titers against VP8* P[8]LI were observed in the group immunized with the nonavalent vaccine compared to mice specifically immunized against this genotype alone. Overall, the development of parenteral vaccines targeting multiple rotavirus genotypes represents a promising strategy in mitigating the global burden of rotavirus-related morbidity and mortality, offering new avenues for disease prevention and control.

Oral HPV infection clearance and acquisition after nonavalent vaccination in men who have sex with men and transgender women: a prospective analysis.

Oral HPV infection is the main risk factor for the development of oropharyngeal carcinoma. Men who have sex with men (MSM), especially if living with HIV (PLWH), are at increased risk of infection and consequently of cancer development. Aim of this study is to evaluate the impact of nonavalent vaccine on oral HPV infection in a cohort of MSM and transgender women (TGW). This prospective study included all MSM and TGW who started nonavalent HPV vaccination from May 2019 to September 2021. Oral rinse was collected before each vaccine administration and after six months of follow up. Descriptive statistics were used. Kaplan Meier probability curves and Cox regression models for HPV acquisition and clearance were calculated. The analysis included 211 individuals (202 MSM and 9 TGW). PLWH were 138 (65.4%). Baseline oral rinse was positive in 30 subjects (14.2%). Positivity rate did not change over time (p = 0.742), even when restricting the analysis only to high-risk genotypes (p = 0.575) and to genotypes covered by vaccine (p = 0.894). The risk to acquire HPV infection was 12.8% at one year and 33.4% at two years after vaccination. The probability to clear the infection was 67.6% at one year and 87.9% at two years. HIV infection had no impact on vaccine efficacy. Age above 45 years was the only factor associated to HPV acquisition (aHR 4.06, 95% CI 1.03-15.98, p = 0.045). Prevalence of oral HPV infection was higher in PLWH, but HIV had no impact on viral clearance or acquisition after vaccination.

EE244 Estimating Treatment Cost Savings of Gender-Neutral Nonavalent HPV Vaccination in Mexico

EE244 Estimating Treatment Cost Savings of Gender-Neutral Nonavalent HPV Vaccination in Mexico

Development of a human papillomavirus (HPV) multiplex immunoassay to profile HPV antibodies.

Neutralizing antibodies (NAbs) are considered the primary mechanism of vaccine-mediated protection against human papillomaviruses (HPV), the causative agent of cervical cancer. However, the minimum level of NAb needed for protection is currently unknown. The HPV pseudovirion-based neutralization assay (PBNA) is the gold standard method for assessing HPV antibody responses but is time-consuming and labor-intensive. With the development of higher valency HPV vaccines, alternative serological assays with the capacity for multiplexing would improve efficiency and output. Here we describe a multiplex bead-based immunoassay to characterize the antibody responses to the seven oncogenic HPV types (HPV16/18/31/33/45/52/58) contained in the current licensed nonavalent HPV vaccine. This assay can measure antibody isotypes and subclasses (total IgG, IgM, IgA1-2, IgG1-4), and can be adapted to measure other antibody features (e.g., Fc receptors) that contribute to vaccine immunity. When tested with serum samples from unvaccinated and vaccinated individuals, we found high concordance between HPV-specific IgG using this multiplex assay and NAbs measured with PBNA. Overall, this assay is high-throughput, sample-sparing, and time-saving, providing an alternative to existing assays for the measurement and characterization of HPV antibody responses.

Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice.

A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon α/β receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 μg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine. In a follow up trial, mice were vaccinated with an adjuvanted nine-serotype multivalent VP2 vaccine in a prime boost strategy and resulted in the desired neutralising antibody titres of 1:320, previously demonstrated to confer protective immunity in IFNAR-/- mice. In addition, the plant-produced VP2 vaccine performed favourably when compared to the commercial vaccine. Here we provide compelling data for a nonavalent VP2-based vaccine candidate, with the VP2 from each serotype being antigenically distinguishable based on LC-MS/MS and ELISA data. This is the first preclinical trial demonstrating the ability of an adjuvanted nonavalent cocktail of soluble, plant-expressed AHS VP2 proteins administered in a prime-boost strategy eliciting high antibody titres against all 9 AHSV serotypes. Furthermore, elevated T helper cells 2 (Th2) and Th1, indicative of humoral and cell-mediated memory T cell immune responses, respectively, were detected in mouse serum collected 14 days after the multivalent prime-boost vaccination. Both Th2 and Th1 may play a role to confer protective immunity. These preclinical immunogenicity studies paved the way to test the safety and protective efficacy of the plant-produced nonavalent VP2 vaccine candidate in the target animals, horses.

Characterization of human papillomavirus genotypes and their coverage in vaccine delivered to Ethiopian women

Cervical cancer is a significant public health concern in Ethiopia. It is mainly caused by persistent infection with the human papillomaviruses. The aim of this study was to assess the relationship between carcinogenic risk of probable, possible and low risk HPV infection and those of cervical intraepithelial neoplasia (CIN) and cervical cancer. A cross sectional study nested from prospective cohort study was conducted in Bahir Dar, northwest Ethiopia. Statistical analyses were performed using SPSSversion 26.0. HPV-16 was associated with a relatively higher risk of CIN II+, (AOR = 15.42; 95% CI 6.81–34.91). In addition, HPV-52, -18, -53 and -58, were significantly associated with an increased risk of CIN II+, (AOR = 7.38 (1.73–31.54), 5.42 (1.61–18.31), 4.08 (1.53–10.87), and 3.17 (1.00–10.03)), respectively. The current study shows high rate of HPV with predominance of HPV-16, -53, -58, -18, -35, and -52. The quadrivalent and nonavalent vaccine had only covered 27.1% and 45% of the circulating HPV genotypes. Ethiopia may need to consider introduction of nonavalent vaccine into the national public health strategy. Polyvalent vaccine which includes the genotypes not covered by existing approved vaccines should be considered.

Cervical Cancer and Human Papilloma Virus (HPV) Vaccines: A primer for General Physicians

India contributes close to 20% of the global cervical cancer burden. This article reviews the preventive strategies against cervical cancer and suggest a few way forward for the prevention of cervical cancer in India. A literature review of online databases (Embase, Google Scholar, PubMed, Scopus) and reports from government websites regarding cervical cancer and HPV vaccination in India was conducted. Currently, four different HPV vaccines are available in India: a bivalent vaccine, a nonavalent vaccine and two quadrivalent vaccines. To reduce India’s cervical cancer burden, the National Technical Advisory Group on Immunization (NTAGI) has advocated the widespread implementation of HPV vaccination. An indigenous HPV vaccine was given market authorisation by the Drugs Controller General of India (DCGI) in July 2022. There is a need to raise awareness regarding the benefits of HPV vaccines in India. The introduction of indigenous HPV vaccine might enhance the supply logistics and may increase the uptake of the vaccine.