anti-HPV Antibodies Research Articles

Characterization of a spray-dried candidate HPV L2-VLP vaccine stored for multiple years at room temperature

HPV infections are associated with human cancers. Although three prophylactic vaccines have been approved to protect against HPV infections, the vaccines require cold-chain storage and may not be suitable for third world countries with less developed refrigeration facilities. We previously developed a bacteriophage L2 virus-like particle (VLP)-based candidate vaccine, which elicited broadly protective antibodies against diverse HPV types. Spray-drying of MS2-16L2 VLPs into a dry powder enhanced the stability of these VLPs. Building on these studies, we assessed the long-term stability and immunogenicity of the spray-dried VLPs. Mice immunized with a single dose of spray-dried MS2-16L2 VLPs, which had been stored for 14 months at room temperature (RT), were partially protected from challenge with a high dose of HPV16, one year after immunization. However, immunization with two doses of MS2-16L2 VLPs stored at RT for 34 months elicited high titer anti-HPV antibodies. More importantly, this group of mice showed significant protection from HPV16, 4 months after immunization. These results suggest that spray-dried MS2-16L2 VLPs retain their effectiveness after long-term storage at RT, and may be suitable in third world countries with less developed refrigeration facilities.

The prevalence of HPV infections in HPV-vaccinated women from the general population.

Currently, three prophylactic HPV vaccines are commercially available to prevent HPV 16/18 infection and associated lesions. The aim of the study was to assess markers of HPV infection in women/girls before vaccination and to ascertain the prevalence and spectrum of post-vaccination HPV types. Three hundred and thirty subjects of which 75 were virgins were enrolled. Before the first dose of the HPV vaccine and 1, 3 and 5 years after the completion of HPV vaccination, the samples for cytology, HPV detection and anti-HPV antibody response were taken. At enrolment, HPV DNA was detected in 38% of sexually active girls/women. At the first, second and third follow-up, HPV DNA was found in 40, 45, and 39% of them. The seroprevalence rates to HPV 6, 11, 16 and 18 in these subjects were 31, 21, 18 and 10%. On the follow-up significantly higher levels of antibodies to HPV 16/18 were found after application of divalent vaccine. Results of the study demonstrate high prevalence of HPV infection in young women. In a substantial number of women, HPV-specific antibodies as well as high-risk HPV types were detected. HPV-specific antibodies were also frequently found in non-sexually active girls. The acquisition of HPV after the onset of sexual life was very fast.

Effect of naturally acquired type-specific serum antibodies against human papillomavirus type 16 infection

BackgroundWhile vaccine-induced antibodies are known to confer protection against incident human papillomavirus (HPV) infection, there is inconsistent data regarding the protective effect of naturally acquired anti-HPV antibodies. ObjectivesTo estimate the protective effect of naturally acquired anti-HPV16 serum antibodies against incident anogenital infection with HPV16 in females aged 20–64 years and to assess whether antibodies influence the persistence/clearance of anogenital HPV16 infection. Study design4432 women attending the organized national cervical cancer screening program in Slovenia were initially enrolled. 2199 and 1848 women had valid HPV DNA results obtained using PCR-based assays and HPV antibody serotyping results obtained using pseudovirion-based serological assay, at baseline and at three-year follow-up, respectively. ResultsBaseline HPV16 seroprevalence was 2.4-fold higher among HPV16 DNA-positive women (55.7% vs. 23.2%; p<0.01). Baseline HPV16 DNA-positive/seronegative women frequently acquired anti-HPV16 antibodies during follow-up (OR=8.2; 95% CI: 3.8–17.8). Baseline anti-HPV16 antibodies persisted at follow-up, irrespective of baseline HPV16 DNA status (OR=40.6; 95% CI: 30.3–54.5). Baseline HPV16 DNA-negative/seropositive women were less likely to acquire HPV16 infection at follow-up (unadjusted OR=0.2; 0.1–0.9). However, the age-adjusted association was non-significant (adjusted OR=0.3; 0.1–1.2). The tendency for protective effect was stronger among women older than 25 years (OR=0.2; 0.03–1.8). Baseline anti-HPV16 antibodies were not associated with persistence/clearance of HPV16 infection at follow-up (OR=0.8; 0.3–1.9). ConclusionsNaturally acquired anti-HPV16 serum antibodies appeared to protect against anogenital HPV16 infection, but this association was at least partially confounded by age. Baseline anti-HPV16 serum antibodies did not influence persistence/clearance of HPV16 infection at follow-up.

Increased Serum Antibody Titer against HPV-16 Antigen in Patients with Behçet's Disease.

Quadrivalent human papillomavirus (HPV) vaccine has been reported to be significantly associated with Behçet's disease (BD). However, no reports have described HPV infection as a possible cause for the development of BD. The objective of this study was to evaluate whether anti-HPV immunoglobulin G (IgG) antibody titer is increased in BD. Serum samples from 93 Korean BD patients, who fulfilled the diagnostic criteria of the International Study Group for BD, were used in an enzyme-linked immunosorbent assay (ELISA). The clinical activity of BD was evaluated at the time of blood sampling. HPV-16 L1 virus-like particle (VLP) antigen was used in this study for the ELISA. Patients with BD had significantly higher antibody titers against HPV-16 (optical density [OD], 0.210–3.675; mean 0.992) than that of healthy controls (OD, 0.248–0.762; mean 0.517; P < 0.001). Using a receiver operating characteristic (ROC) analysis, a cut-off value of 0.578 OD for the anti-HPV antibody titer was determined that differentiated BD patients from healthy controls. When we compared the clinical features of BD between the 2 groups, articular involvement of BD was more likely in patients with an anti-HPV-16 antibody titer < 0.578 OD (P = 0.035). In addition, patients with an anti-HPV-16 antibody titer < 0.578 were significantly younger than those with a titer ≥ 0.578 OD. HPV itself may be a possible extrinsic triggering infectious agent causing the development of BD.

Gender and age-specific seroprevalence of human papillomavirus 16 and 18 in general population in Tehran, Iran.

The assessment of the gender and age-specific seroprevalence of human papillomavirus (HPV) is essential for planning of HPV vaccine implementation into the preventive programs. In this study, we aimed to determine the age-specific seroprevalence of HPV-16 and 18 in both males and females in Tehran, Iran. Three hundred and seventy-eight women (10-35years) and 162 men (10-25years) from Tehran, Iran, were enrolled. Anti-HPV IgG antibodies against HPV-16 and HPV-18 were detected by ELISA using papillomavirus type 16 and 18 L1-capsids as antigen. HPV-16 antibody was detected in 15.6 and 13.6% of women and men, respectively. Antibody against HPV-18 was found positive in 12.7 and 8% of women and men, respectively. The highest seroprevalence of HPV-16 and 18 were seen in women aged 26-30years (22.2 and 19.4%, respectively), and the lowest HPV-16 and 18 seropositivity rates were seen in males and females aged 10-15years (9.3 and 1.9%, respectively). In our cohort of study, in males, both anti-HPV-16 and 18 increased after age 15years, peaking in men aged 21-25years. In women, both HPV-16 and 18 seropositivity increased after 15years, declined at 21-25years, peaked in women aged 26-30years and again decreased after 30years. Our data showed increasing exposure rate to high-risk HPV vaccine types in our studied population over 15years of age. In order to prevent the HPV-related cancers, implementation of HPV vaccine into the national immunization program in Iran and vaccination of females and males less than 15years of age are suggested.

Progress in clinical immunology of human papillomavirus vaccines

Persistent human papillomavirus (HPV) infections have been identified as the main causes of cervical cancer. HPV vaccination has become the preferred option for the prevention of cervical cancer and pre-cancerous lesions. The effectiveness of vaccination could be indirectly reflected in the level of anti-HPV antibody. Therefore, immunogenicity analysis plays an important role in the clinical evaluation of HPV vaccines. Up to now, three HPV vaccines including Cervarix®, Gardasil® and Gardasil® 9 have been licensed in many countries, but a standard assay for assessing the immunogenicity of HPV vaccines has not been established. Currently, pseudovirion-based neutralization assay (PBNA), ELISA and competitive luminex immunoassay(cLIA) are the three major assays widely used in clinical trials of HPV vaccines. This study reviewed the traits of the three assays, the immunogenicity and durability of the three HPV vaccines, as well as the immune responses induced in different populations. Key words: Human papillomavirus; Vaccine; Immunogenicity; Cervical cancer

Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil.

Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil+pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, p=0.009; Gardasil, p=0.025; Gardasil+Pt, p=0.005). The increase in floating time was already highly significant at 4.5months of age for the Gardasil and Gardasil+Pt group (p≤0.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil+Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes.

Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children

AimThe aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. MethodsA multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5–18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. ResultsFifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. ConclusionImmunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children.Clinical trial registration:NCT02263703 (ClinicalTrials.gov)

Production of Human papillomavirus pseudovirions in plants and their use in pseudovirion-based neutralisation assays in mammalian cells.

Human papillomaviruses (HPV) cause cervical cancer and have recently also been implicated in mouth, laryngeal and anogenital cancers. There are three commercially available prophylactic vaccines that show good efficacy; however, efforts to develop second-generation vaccines that are more affordable, stable and elicit a wider spectrum of cross-neutralising immunity are still ongoing. Testing antisera elicited by current and candidate HPV vaccines for neutralizing antibodies is done using a HPV pseudovirion (PsV)-based neutralisation assay (PBNA). PsVs are produced by transfection of mammalian cell cultures with plasmids expressing L1 and L2 capsid proteins, and a reporter gene plasmid, a highly expensive process. We investigated making HPV-16 PsVs in plants, in order to develop a cheaper alternative. The secreted embryonic alkaline phosphatase (SEAP) reporter gene and promoter were cloned into a geminivirus-derived plant expression vector, in order to produce circular dsDNA replicons. This was co-introduced into Nicotiana benthamiana plants with vectors expressing L1 and L2 via agroinfiltration, and presumptive PsVs were purified. The PsVs contained DNA, and could be successfully used for PBNA with anti-HPV antibodies. This is the first demonstration of the production of mammalian pseudovirions in plants, and the first demonstration of the potential of plants to make DNA vaccines.

Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor.

The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5+/6+) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients.

A Serological Epidemiological Survey of Antibodies against 4 HPV Subtypes in Uygur Women in Xinjiang.

This study evaluated the distribution of antibodies against 4 human papillomavirus (HPV) subtypes and their related factors among Uygur women in Xinjiang. A cross-sectional study was conducted from March 2006 to May 2007 involving 883 Uygur women aged 17-54 years living in Yutian County. Demographic indicators, disease history, sexual behavior history, and other parameters were recorded at the interview using a questionnaire. A fluorescence detection method was used to quantify anti-HPV6, -11, -16, and -18 antibodies in venous blood serum. The rate of positive detection of any anti-HPV antibody (anti-HPV6, -11, -16, and -18) in the study population was 13.4%, and the individual positivity rates were 9.5%, 2.6%, 4.3%, and 0.7%, respectively. Peak rates of positivity for the anti-HPV16 antibody were found in women who were 36-40 and 46-50 years old. Seroprevalence of HPV16, which is high-risk for cervical cancer, was associated with the numbers of sexual partners. The rate of infection with high-risk HPV was low among Uygur women from rural areas, although there is a high incidence of cervical cancer in this group. Loyalty to one sexual partner decreased the risk of high-risk HPV infection. This study may provide useful reference data for the prevention and treatment of HPV and cervical cancer and for the application of HPV vaccines.

Observations on the expression of human papillomavirus major capsid protein in HeLa cells.

BackgroundThe goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells.MethodsHPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control.ResultsHPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80–85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells.ConclusionsThe inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

Seroprevalence and awareness of human papillomavirus infection and cervical cancer screening results among reproductive-aged Georgian women

IntroductionAs is the case in many developing countries, more than half of the new cervical cancer cases in Georgia are late-stage diagnoses, thus reducing the opportunity for effective treatment. A...

P29 The role of HPV in cervical lymph node metastases from squamous cell carcinoma

Human papillomavirus (HPV) infection is a risk factor for various cancer types, including head and neck squamous cell carcinoma (HNSCC). HPV-positive HNSCC show better survival compared to HPV-negative HNSCC despite their frequent early metastatic spread to cervical lymph nodes. Patients initially presenting only with a cervical lymph node metastasis (CLNM) during work-up are frequently diagnosed with HNSCC. In a few CLNM cases no primary tumor is detected. Aggressive multimodal treatment of these cancers of unknown primary site (CUP) often leads to substantial side effects and loss of quality of life. Recent studies provide evidence that the HPV status may have a prognostic value in CUP and may serve as a predictor for oropharyngeal localization of the primary tumor. In a multinational retrospective study (Heidelberg, Barcelona, Treviso) we want to determine the prevalence of HPV-driven SCC in CLNM with unknown or identified primary tumor. Presence of 51 mucosal HPV types will be analyzed in fresh-frozen and/or formalin-fixed paraffin-embedded tissue from lymph node metastases and, if available, the corresponding primary tumor. To identify truly HPV-driven cases additional markers including viral load, E6*I oncogene mRNA and expression levels of the cellular proteins p16INK4a, p53 and pRb will be determined. In addition, if fresh-frozen tissue and serum are available viral transformation-associated RNA patterns and anti-HPV antibodies, respectively, will be analyzed. Results of ongoing HPV status analyses will be presented. These data will be correlated with clinical parameters to assess, whether active HPV involvement is associated with a better prognosis and may help to direct the search for the primary tumor towards the oropharynx. Furthermore, we want to study pairs of HPV-driven oropharyngeal tumors and the corresponding cervical lymph node metastases by comparing the HPV status and integration patterns. The study is open for participation of additional clinical collaborators.

A comparative study of two different assay kits for the detection of secreted alkaline phosphatase in HPV antibody neutralization assays

To assess immunogenicity and development of antibodies in the context of vaccination, it is critical to quantify titers of neutralizing antibodies. We have been employing the 293TT cell-based neutralization assay system to quantify anti-HPV neutralizing antibodies. In this system, human papillomavirus (HPV) pseudovirion (PsV) particles encapsidating secreted alkaline phosphatase (SEAP) gene are used to measure infection of 293TT cells in 72-hr cell-culture supernatants. SEAP has traditionally been measured by Great EscAPe™ SEAP Chemiluminescence Kit 2.0 (GE). To reduce the cost, and to potentially increase efficiency, we sought a cheaper kit with better detection capability. Performance characteristics of the newer chemiluminescence kit, ZiVa® Ultra SEAP Plus Assay (Ziva) and GE were compared using the 293TT system. Dose titration of HPV PsV 16 or 18 showed that signal-to-noise ratios at 48 and 72 hr post-infection were higher for ZiVa at nearly all doses. ZiVa was superior to GE as it was able to detect SEAP at 48 hr, as well as when lower numbers of 293TT cells were used. The ability of ZiVa to quantitate HPV-16 and -18 neutralizing antibody titers was tested using sera from Cervarix® immunized individuals. Spearman rank correlational analyses showed excellent correlations between the titers obtained with ZiVa and GE for anti-HPV16 (r = 0.9822, p < 0.0001) and anti-HPV18 (r = 0.9832, p < 0.0001) antibodies. We concluded that ZiVa is superior to GE in detecting SEAP, and the antibody titers in sera of vaccinated individuals were similar to those obtained with GE. Thus, Ziva is a suitable alternative to GE.

The levels of anti-HPV16/18 and anti-HPV31/33/35/45/52/58 antibodies among AS04-adjuvanted HPV16/18 vaccinated and non-vaccinated Ugandan girls aged 10-16 years.

BackgroundData on Human Papilloma virus (HPV) vaccine immune response in sub-Saharan Africa is still sparse yet such knowledge is critical for optimal implementation and monitoring of HPV vaccines. Our primary objective was to evaluate levels of anti-HPV-16/18 antibodies and six other ‘high risk’ HPV (hrHPV) types among the vaccinated and unvaccinated Ugandan girls.MethodsWe conducted a cross sectional study among AS04-adjuvanted HPV-16/18 vaccinated and unvaccinated school girls aged 10–16 years in Western Uganda using purposive sampling. The vaccinated girls were at 18 months post vaccination. After consenting and assenting, data was collected using interviewer administered questionnaires for demographics and sexual history. Blood was drawn from which serum samples were analysed by the multiplex HPV serology technology to determine anti-HPV antibody levels to HPV-16/18 and six other hrHPV types (31, 33, 35, 45, 52 and 58). The antibody levels were expressed as Median Fluorescent Intensity (MFI).A total of 207 vaccinated [mean age 13.1 years (SD 1.5); range 10-16 years] and 197 unvaccinated girls [mean age 13.6 years (SD 1.3); range 10-16 years] participated in the study. Sexual activity was self reported among 14/207 (6.8%) vaccinated and 5/197 (2.5%) unvaccinated girls. The MFI levels for HPV-16 and HPV-18 were 15 and 20 times higher respectively in the vaccinated girls than in the unvaccinated girls. HPV-16 mean MFI level was 4691(SD 1812; 95% CI: 4438-4958) among the vaccinated compared to 218 (SD 685; 95% CI: 190-252) among the unvaccinated girls. For HPV-18 the mean MFI level was 1615 (SD 1326; 95% CI: 1470-1776) among the vaccinated compared to MFI 103 (SD 506; 95% CI: 88 -121) among unvaccinated girls.In addition antibody levels to non vaccine hrHPV types (31, 33, 35, 45, 52 and 58) were all significantly higher in the vaccinated group than in the unvaccinated group (p<0.01).ConclusionThe AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18 and other non-vaccine hrHPV types compared to the unvaccinated girls. This may translate into protection against HPV-16/18 and other hrHPV types.

Nonlinear Fractional Polynomials for Estimating Long-Term Persistence of Induced Anti-HPV Antibodies: A Hierarchical Bayesian Approach

When the true relationship between a covariate and an outcome is nonlinear, one should use a nonlinear mean structure that can take this pattern into account. In this article, the fractional polynomial modeling framework, which assumes a prespecified set of powers, is extended to a nonlinear fractional polynomial framework (NLFP). Inferences are drawn in a Bayesian fashion. The proposed modeling paradigm is applied to predict the long-term persistence of vaccine-induced anti-HPV antibodies. In addition, the subject-specific posterior probability to be above a threshold value at a given time is calculated. The model is compared with a power-law model using the deviance information criterion (DIC). The newly proposed model is found to fit better than the power-law model. A sensitivity analysis was conducted, from which a relative independence of the results from the prior distribution of the power was observed. Supplementary materials for this article are available online.

Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil(®)): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts.

Quadrivalent human papillomavirus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil(®); Silgard(®)) is composed of virus-like particles formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16 and 18. It is indicated for use from the age of 9years as a two- or three-dose vaccination course over 6months for the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts caused by the vaccine HPV types. In placebo-controlled trials, quadrivalent HPV vaccine provided high-level protection against infection or disease caused by the vaccine HPV types over 2-4years in females aged 15-45years who were negative for the vaccine HPV types, and provided a degree of cross-protection against certain non-vaccine HPV types. The vaccine also provided high-level protection against persistent infection, anogenital precancerous lesions and genital warts caused by the vaccine HPV types over 3years in susceptible males aged 16-26years. Protection has been demonstrated for up to 8years. In subjects who were negative for the vaccine HPV types, high seroconversion rates and high levels of anti-HPV antibodies were observed in females of all age ranges from 9 to 45years and in males aged 9-26years. The vaccine was generally well tolerated and was usually predicted to be cost effective in girls and young women. Therefore, quadrivalent HPV vaccine offers an effective means to substantially reduce the burden of HPV-related anogenital disease in females and males, particularly cervical cancer and genital warts.

FRI0421 Immune Effects of Human Papilloma Virus (HPV) Immunization in Patients with Systemic Lupus Erythematosus (SLE)

BackgroundWomen with SLE show an increased risk for HPV infection and development of precancerous lesions. Although HPV vaccine is safe and effective in healthy females, there are limited data on...

A high-performance thioredoxin-based scaffold for peptide immunogen construction: proof-of-concept testing with a human papillomavirus epitope.

Escherichia coli thioredoxin has been previously exploited as a scaffold for the presentation/stabilization of peptide aptamers as well as to confer immunogenicity to peptide epitopes. Here we focused on other key features of thioredoxin that are of general interest for the production of safer and more effective peptide immunogens, such as a high thermal stability, lack of cross-reactivity and a low-cost of production. We identified thioredoxin from the archaebacterium Pyrococcus furiosus (PfTrx) as a novel scaffold meeting all the above criteria. PfTrx is a highly thermostable and protease-resistant scaffold with a strong (poly)peptide solubilisation capacity. Anti-PfTrx antibodies did not cross-react with mouse, nor human thioredoxin. Untagged PfTrx bearing a previously identified HPV16-L2 peptide epitope was obtained in a >90% pure form with a one-step thermal purification procedure and effectively elicited the production of neutralizing anti-HPV antibodies. We thus propose PfTrx as a superior, general-purpose scaffold for the construction of safe, stable, and low-cost peptide immunogens.