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John T Schiller - One of the best experts on this subject based on the ideXlab platform.
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impact of human Papillomavirus hpv 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment
American Journal of Obstetrics and Gynecology, 2016Co-Authors: Allan Hildesheim, Paula Gonzalez, Aimee R Kreimer, Sholom Wacholder, John Schussler, Ana Cecilia Rodriguez, Carolina Porras, Mark Schiffman, Mary K Sidawy, John T SchillerAbstract:Background Human Papillomavirus vaccines prevent human Papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human Papillomavirus-associated lesion is not fully understood. Objectives To determine whether human Papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. Study Design We included 1711 women (18−25 years) with carcinogenic human Papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human Papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human Papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human Papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human Papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. Results Median follow-up was 56.7 months (women with human Papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human Papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human Papillomavirus types present at enrollment. Vaccine efficacy for human Papillomavirus 16/18 clearance and against human Papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human Papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human Papillomavirus 16/18, human Papillomavirus 31/33/45, and oncogenic human Papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval −43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. Conclusion We find no evidence for a vaccine effect on the fate of detectable human Papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies.
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murine skin and vaginal mucosa are similarly susceptible to infection by pseudovirions of different Papillomavirus classifications and species
Virology, 2012Co-Authors: Alessandra Handisurya, Christopher B Buck, Cynthia D Thompson, Kihyuck Kwak, Douglas R Lowy, Richard B S Roden, John T SchillerAbstract:Abstract Depending upon viral genotype, productive Papillomavirus infection and disease display preferential tropism for cutaneous or mucosal stratified squamous epithelia, although the mechanisms are unclear. To investigate Papillomavirus entry tropism, we used reporter pseudovirions based on various cutaneous and mucosal Papillomavirus species, including the recently identified murine Papillomavirus. Pseudovirus transduction of BALB/c mice was examined using an improved murine skin infection protocol and a previously developed cervicovaginal challenge model. In the skin, HPV5, HPV6, HPV16, BPV1 and MusPV1 pseudovirions preferentially transduced keratinocytes at sites of trauma, similar to the genital tract. Skin infection, visualized by in vivo imaging using a luciferase reporter gene, peaked between days 2–3 and rapidly diminished for all pseudovirion types. Murine cutaneous and genital tissues were similarily permissive for pseudovirions of HPV types 5, 6, 8, 16, 18, 26, 44, 45, 51, 58 and animal Papillomaviruses BPV1 and MusPV1, implying that Papillomavirus' tissue and host tropism is governed primarily by post-entry regulatory events in the mouse.
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heparan sulfate independent cell binding and infection with furin precleaved Papillomavirus capsids
Journal of Virology, 2008Co-Authors: Douglas R Lowy, John T SchillerAbstract:Papillomavirus infection normally involves virion binding to cell surface heparan sulfate proteoglycans (HSPGs). However, we found that human Papillomavirus type 16 pseudovirions efficiently bound and infected cells lacking HSPGs if their L2 capsid protein was precleaved by furin, a cellular protease required for infection. The inability of pseudovirions to efficiently bind and infect cultured primary keratinocytes was also overcome by furin precleavage, suggesting that the defect involves altered HSPG modification. We conclude that the primary function of HSPG binding is to enable cell surface furin cleavage of L2 and that binding to a distinct cell surface receptor(s) is a subsequent step of Papillomavirus infection.
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reactivity of human sera in a sensitive high throughput pseudovirus based Papillomavirus neutralization assay for hpv16 and hpv18
Virology, 2004Co-Authors: Diana V Pastrana, Christopher B Buck, Yuk Ying S Pang, Cynthia D Thompson, Philip E Castle, Peter C Fitzgerald, Susanne K Kjaer, Douglas R Lowy, John T SchillerAbstract:Abstract Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated for human Papillomavirus (HPV)16, HPV18, and bovine Papillomavirus 1 (BPV1). SEAP pseudoviruses were produced by transient transfection of codon-modified Papillomavirus structural genes into an SV40 T antigen expressing line derived from 293 cells, yielding sufficient pseudovirus from one flask for thousands of titrations. In a 96-well plate format, in this initial characterization, the assay was reproducible and appears to be as sensitive as, but more specific than, a standard Papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The neutralization assay detected type-specific HPV16 or HPV18 neutralizing antibodies (titers of 160–10240) in sera of the majority of a group of women infected with the corresponding HPV type, but not in virgin women. Sera from HPV16 VLP vaccinees had high anti-HPV16 neutralizing titers (mean: 45000; range: 5120–163840), but no anti-HPV18 neutralizing activity. The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies.
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Papillomavirus l1 major capsid protein self assembles into virus like particles that are highly immunogenic
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Reinhard Kirnbauer, John T Schiller, Frank P Booy, Naiqian Cheng, D R LowyAbstract:Abstract Infection by certain human Papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of Papillomavirus virions has been hampered by the inability to efficiently propagate the viruses in cultured cells. For instance, it has not been established whether the major capsid protein L1 alone is sufficient for virus particle assembly. In addition, it is not known whether L1, L2 (the minor capsid protein), or both present the immunodominant epitopes required for induction of high-titer neutralizing antibodies. We have expressed the L1 major capsid proteins of bovine Papillomavirus type 1 and human Papillomavirus type 16 in insect cells via a baculovirus vector and analyzed their conformation and immunogenicity. The L1 proteins were expressed at high levels and assembled into structures that closely resembled Papillomavirus virions. The self-assembled bovine Papillomavirus L1, in contrast to L1 extracted from recombinant bacteria or denatured virions, also mimicked intact bovine Papillomavirus virions in being able to induce high-titer neutralizing rabbit antisera. These results indicate that L1 protein has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent Papillomavirus infection.
Joakim Dillner - One of the best experts on this subject based on the ideXlab platform.
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cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma population based nested case control study
BMJ, 2019Co-Authors: Jiayao Lei, Bengt Andrae, Alexander Ploner, Camilla Lagheden, Carina Eklund, Sara Nordqvist Kleppe, Jiangrong Wang, Fang Fang, Joakim DillnerAbstract:Abstract Objectives To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human Papillomavirus status of ASC and RICC. Design Nationwide, population based, nested case-control study. Setting Sweden. Participants All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling. Main outcome measures Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human Papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks. Results Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human Papillomavirus was detected in 148/211 (70%) cases with valid human Papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human Papillomavirus was similar, compared with women who did not attend any test. Conclusions Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human Papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.
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regular disappearance of the human Papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser
American Journal of Obstetrics and Gynecology, 2000Co-Authors: Lennart Kjellberg, Goran Wadell, Frank Bergman, Monica Isaksson, Tord Angstrom, Joakim DillnerAbstract:OBJECTIVE: We wished to evaluate the effectiveness of treatment of cervical dysplasia by laser conization in relation to persistence of human Papillomavirus after treatment. STUDY DESIGN: Of 203 women referred to colposcopy because of an abnormal Papanicolaou smear, 149 women could be followed up for 3 years. A total of 108 women were treated by carbon dioxide laser excision, 4 women were treated by carbon dioxide laser evaporation, and 37 women were merely followed up. Cervical samples were taken before treatment and at follow-up 3 years later and were analyzed by nested general primer polymerase chain reaction for human Papillomavirus deoxyribonucleic acid. RESULTS: Among women treated by laser conization, 82 (73.2%) had positive results for human Papillomavirus deoxyribonucleic acid before treatment. Three women (2.7%) had a positive finding at follow-up, but no woman had the same human Papillomavirus type on both occasions. Eighty-eight women had grade 1 to grade 3 cervical intraepithelial neoplasia before treatment, whereas during follow-up only 2 squamous cells atypias were found. CONCLUSION: The human Papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human Papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human Papillomavirus should be favored.
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Conization for cervical intraepithelial neoplasia is followed by disappearance of human Papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human Papillomavirus antigens.
American journal of obstetrics and gynecology, 1996Co-Authors: Kristina Elfgren, Peter Bistoletti, Lena Dillner, Jan M. M. Walboomers, Chris J.l.m. Meijer, Joakim DillnerAbstract:Abstract OBJECTIVE: Our purpose was to investigate whether conization for cervical intraepithelial neoplasia eliminates human Papillomavirus deoxyribonucleic acid and affects the levels of serum and cervical mucus antibodies against human Papillomavirus antigens. STUDY DESIGN: Analysis of paired cervical brush and serum samples taken from 23 women with cervical intraepithelial neoplasia before and 16 to 27 months after conization was performed for presence of human Papillomavirus deoxyribonucleic acid by polymerase chain reaction and for human Papillomavirus antibodies by enzyme-linked immunosorbent assay. RESULTS: Four women had recurrent cervical intraepithelial neoplasia, whereas 19 women were disease free. Eighteen of 23 women were positive for human Papillomavirus deoxyribonucleic acid before treatment. At follow-up only the 4 women with recurrent cervical intraepithelial neoplasia were positive. Serum immunoglobulin G levels and A levels and immunoglobulin A levels in cervical mucus against most of the tested human Papillomavirus antigens had declined at follow-up. CONCLUSIONS: Human Papillomavirus deoxyribonucleic acid was regularly eliminated and human Papillomavirus antibody levels, especially local immunoglobulin A, declined after efficient treatment, suggesting that conization may be effective for treating the underlying human Papillomavirus infection. (AM J OBSTET GYNECOL 1996;174:937-42.)
Janine T Bryan - One of the best experts on this subject based on the ideXlab platform.
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Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women
Pediatrics, 2006Co-Authors: Stan L Block, Carlos Sattler, Katherine E.d. Giacoletti, Steven A. Rusche, Suzanne Lukac, Terry Nolan, Colin D Marchant, Eliav Barr, Xavier Castellsague, Janine T BryanAbstract:OBJECTIVE. Prophylactic vaccination of 16- to 23-year-old females with a quadrivalent human Papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine has been shown to prevent type-specific human Papillomavirus infection and associated clinical disease. We conducted a noninferiority immunogenicity study to bridge the efficacy findings in young women to preadolescent and adolescent girls and boys, who represent a primary target for human Papillomavirus vaccination. METHODS. We enrolled 506 girls and 510 boys (10–15 years of age) and 513 females (16–23 years of age). Participants were vaccinated on day 1, at month 2, and at month 6, and serology testing was performed on day 1 and at months 3 and 7 on blinded samples. Neutralizing antibody concentrations were determined using type-specific immunoassays and summarized as geometric mean titers and seroconversion rates. Vaccine tolerability also was assessed. RESULTS. By month 7, seroconversion rates were ≥99% for all 4 human Papillomavirus types in each group. By month 7, compared with women, anti–human papilloma virus geometric mean titers in girls or boys were noninferior and were 1.7- to 2.7-fold higher. Most (>97%) injection-site adverse events were mild to moderate in intensity. Significantly more boys (13.8%) and girls (12.8%) than women (7.3%) reported fevers ≥37.8°C within 5 days of vaccination. Most (96.4%) fevers were mild ( CONCLUSIONS. Noninferior immunogenic responses to all 4 human Papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human Papillomavirus vaccination programs. This vaccine generally was well tolerated.
Marc Van Ranst - One of the best experts on this subject based on the ideXlab platform.
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Genetic characterization of the first chiropteran Papillomavirus, isolated from a basosquamous carcinoma in an Egyptian fruit bat: the Rousettus aegyptiacus Papillomavirus type 1.
Veterinary microbiology, 2006Co-Authors: Annabel Rector, Koenraad Van Doorslaer, Christy A. Mcknight, Annabel G. Wise, Roger K. Maes, Matti Kiupel, Sara Mostmans, Marc Van RanstAbstract:The complete genomic DNA of a novel Papillomavirus (PV) was isolated from a basosquamous carcinoma on the wing of an Egyptian fruit bat (Rousettus aegyptiacus). Initial short sequences of the E1 and L1 genes of this virus were retrieved by PCR with degenerate Papillomavirus-specific primers, and the entire R. aegyptiacus Papillomavirus type 1 (RaPV-1) DNA was then amplified by long template PCR, cloned and sequenced with a transposon insertion method. The RaPV-1 genome counts 7970 basepairs and contains the typical Papillomavirus open reading frames (ORF) (E1, E2, E4, E6, E7, L1 and L2). Based on a concatenated alignment of the E1, E2, L1 and L2 open reading frames of RaPV-1 and 46 other human and animal Papillomavirus type species, a neighbor-joining phylogenetic tree was constructed. This phylogenetic analysis shows that RaPV-1 has a close-to-root position in the Papillomavirus evolutionary tree. Since RaPV-1 is only distantly related to other Papillomaviruses (with maximally 50% nucleotide sequence identity across the L1 open reading frame), it cannot be assigned to one of the existing Papillomavirus genera and therefore represents the first member of a novel, as yet unnamed, close-to-root Papillomavirus genus. This is the first time a Papillomavirus has been isolated and characterized from a member of the Chiroptera order.
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Papillomavirus-ASSOCIATED BASOSQUAMOUS CARCINOMA IN AN EGYPTIAN FRUIT BAT (ROUSETTUS AEGYPTIACUS)
Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians, 2006Co-Authors: Christy A. Mcknight, Annabel Rector, Marc Van Ranst, Annabel G. Wise, Roger K. Maes, Christopher Howe, Matti KiupelAbstract:A 5-yr-old female Egyptian fruit bat (Rousettus aegyptiacus) had a small raised pigmented mass removed from the lateral canthus of the left eye. Six additional variably sized, raised, smooth to cauliflower-like skin masses were observed randomly distributed throughout the left wing membranes. Four masses were removed and diagnosed microscopically as basosquamous carcinomas and papillomas. Additional masses, removed 6 mo and 1 yr later, showed bony invasion and squamous differentiation. Immunohistochemistry detected positive intranuclear staining for bovine Papillomavirus antibody in all samples. Polymerase chain reaction done on DNA extracts from formalin-fixed, paraffin-embedded tumor tissue amplified a 450 base-pair segment analogous to the L1 region of human Papillomavirus types 96 and 5. Basic Local Alignment Search Tool analysis of sequenced amplicons suggests a novel chiropteran Papillomavirus. To our knowledge, this is the first report of Papillomavirus-associated carcinoma in a chiropteran species.
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Isolation and cloning of the raccoon (Procyon lotor) Papillomavirus type 1 by using degenerate Papillomavirus-specific primers.
The Journal of general virology, 2005Co-Authors: Annabel Rector, John P Sundberg, Koenraad Van Doorslaer, Mads Bertelsen, Ian K Barker, Rolf-arne Olberg, Philippe Lemey, Marc Van RanstAbstract:Partial sequences of a novel Papillomavirus were amplified from a cutaneous lesion biopsy of a raccoon (Procyon lotor), by using PCR with degenerate Papillomavirus-specific primers. The Procyon lotor Papillomavirus type 1 (PlPV-1) DNA was amplified with long template PCR in two overlapping fragments, together encompassing the entire genome, and the complete PlPV-1 genomic sequence was determined. The PlPV-1 genome consists of 8170 bp, and contains the typical papillomaviral open reading frames, encoding five early proteins and two late capsid proteins. Besides the classical non-coding region (NCR1) between the end of L1 and the start of E6, PlPV-1 contains an additional non-coding region (NCR2) of 1065 bp between the early and late protein region, which has previously also been described for the canine oral Papillomavirus (COPV) and the Felis domesticus Papillomavirus (FdPV-1). Phylogenetic analysis places PlPV-1 together with COPV and FdPV-1 in a monophyletic branch which encompasses the Lambda Papillomavirus genus.
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avian Papillomaviruses the parrot psittacus erithacus Papillomavirus pepv genome has a unique organization of the early protein region and is phylogenetically related to the chaffinch Papillomavirus
BMC Microbiology, 2002Co-Authors: Ruth Tachezy, Bennett A Jenson, John P Sundberg, Annabel Rector, Marta Havelkova, Elke Wollants, Pierre Fiten, Ghislain Opdenakker, Marc Van RanstAbstract:Background: An avian Papillomavirus genome has been cloned from a cutaneous exophytic papilloma from an African grey parrot (Psittacus erithacus). The nucleotide sequence, genome organization, and phylogenetic position of the Psittacus erithacus Papillomavirus (PePV) were determined. This PePV sequence represents the first complete avian Papillomavirus genome defined. Results: The PePV genome (7304 basepairs) differs from other Papillomaviruses, in that it has a unique organization of the early protein region lacking classical E6 and E7 open reading frames. Phylogenetic comparison of the PePV sequence with partial E1 and L1 sequences of the chaffinch (Fringilla coelebs) Papillomavirus (FPV) reveals that these two avian Papillomaviruses form a monophyletic cluster with a common branch that originates near the unresolved center of the Papillomavirus evolutionary tree. Conclusions: The PePV genome has a unique layout of the early protein region which represents a novel prototypic genomic organization for avian Papillomaviruses. The close relationship between PePV and FPV, and between their Psittaciformes and Passeriformes hosts, supports the hypothesis that Papillomaviruses have co-evolved and speciated together with their host species throughout evolution.
Carlos Sattler - One of the best experts on this subject based on the ideXlab platform.
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safety and immunogenicity of a quadrivalent human Papillomavirus types 6 11 16 and 18 vaccine in hiv infected children 7 to 12 years old
Journal of Acquired Immune Deficiency Syndromes, 2010Co-Authors: Myron J Levin, Carlos Sattler, Annabarbara Moscicki, Linye Song, Terrence Fenton, William A Meyer, Jennifer S Read, Edward Handelsman, B F Nowak, Alfred J SaahAbstract:Background Quadrivalent human Papillomavirus vaccine (QHPV) is >95% effective in preventing infection with vaccine-type human Papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children.
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Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women
Pediatrics, 2006Co-Authors: Stan L Block, Carlos Sattler, Katherine E.d. Giacoletti, Steven A. Rusche, Suzanne Lukac, Terry Nolan, Colin D Marchant, Eliav Barr, Xavier Castellsague, Janine T BryanAbstract:OBJECTIVE. Prophylactic vaccination of 16- to 23-year-old females with a quadrivalent human Papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine has been shown to prevent type-specific human Papillomavirus infection and associated clinical disease. We conducted a noninferiority immunogenicity study to bridge the efficacy findings in young women to preadolescent and adolescent girls and boys, who represent a primary target for human Papillomavirus vaccination. METHODS. We enrolled 506 girls and 510 boys (10–15 years of age) and 513 females (16–23 years of age). Participants were vaccinated on day 1, at month 2, and at month 6, and serology testing was performed on day 1 and at months 3 and 7 on blinded samples. Neutralizing antibody concentrations were determined using type-specific immunoassays and summarized as geometric mean titers and seroconversion rates. Vaccine tolerability also was assessed. RESULTS. By month 7, seroconversion rates were ≥99% for all 4 human Papillomavirus types in each group. By month 7, compared with women, anti–human papilloma virus geometric mean titers in girls or boys were noninferior and were 1.7- to 2.7-fold higher. Most (>97%) injection-site adverse events were mild to moderate in intensity. Significantly more boys (13.8%) and girls (12.8%) than women (7.3%) reported fevers ≥37.8°C within 5 days of vaccination. Most (96.4%) fevers were mild ( CONCLUSIONS. Noninferior immunogenic responses to all 4 human Papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human Papillomavirus vaccination programs. This vaccine generally was well tolerated.
