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Dive into the research topics where Darron R. Brown is active.

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Featured researches published by Darron R. Brown.


Lancet Oncology | 2005

Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

Luisa L. Villa; Ronaldo Lúcio Rangel Costa; Carlos Alberto Petta; Rosires Pereira de Andrade; Kevin A. Ault; Anna R. Giuliano; Cosette M. Wheeler; Laura A. Koutsky; Christian Malm; Matti Lehtinen; Finn Egil Skjeldestad; Sven Eric Olsson; Margareta Steinwall; Darron R. Brown; Robert J. Kurman; Brigitte M. Ronnett; Mark H. Stoler; Alex Ferenczy; Diane M. Harper; Gretchen M. Tamms; Jimmy Yu; Lisa Lupinacci; Radha Railkar; Frank J. Taddeo; Kathrin U. Jansen; Mark T. Esser; Heather L. Sings; Alfred Saah; Eliav Barr

BACKGROUND A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). METHODS 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. FINDINGS Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. INTERPRETATION A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.


Obstetrics & Gynecology | 2006

Efficacy of Human Papillomavirus-16 Vaccine to Prevent Cervical Intraepithelial Neoplasia A Randomized Controlled Trial

Constance Mao; Laura A. Koutsky; Kevin A. Ault; Cosette M. Wheeler; Darron R. Brown; Dorothy J. Wiley; Frances B. Alvarez; Oliver M. Bautista; Kathrin U. Jansen; Eliav Barr

OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2–3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16–23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 &mgr;g HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2–3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65–100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88–98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milli-Merck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128–150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2–3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer. LEVEL OF EVIDENCE: I


The Journal of Infectious Diseases | 2005

A Longitudinal Study of Genital Human Papillomavirus Infection in a Cohort of Closely Followed Adolescent Women

Darron R. Brown; Marcia L. Shew; Brahim Qadadri; Nicole Neptune; Maria Vargas; Wanzhu Tu; Beth E. Juliar; Timothy Breen; J. Dennis Fortenberry

BACKGROUND We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women. METHODS A cohort of 60 adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subject. RESULTS HPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic--or high-risk (HR)--HPV types were detected in 38.6% of specimens, and nononcogenic--or low-risk (LR)--types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection. CONCLUSIONS The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.


BMJ | 2010

Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.

Joakim Dillner; Susanne K. Kjaer; Cosette M. Wheeler; Kristján Sigurdsson; Ole Erik Iversen; Mauricio Hernandez-Avila; Gonzalo Perez; Darron R. Brown; Laura A. Koutsky; Eng Tay; Patricia J. García; Kevin A. Ault; Suzanne M. Garland; Sepp Leodolter; Sven Eric Olsson; Grace W.K. Tang; Daron G. Ferris; Jorma Paavonen; Matti Lehtinen; Marc Steben; F. Xavier Bosch; Elmar A. Joura; Slawomir Majewski; Nubia Muñoz; Evan R. Myers; Luisa L. Villa; Frank J. Taddeo; Christine Roberts; Amha Tadesse; Janine T. Bryan

Objectives To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months’ follow-up. Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations NCT00092521 and NCT00092534.


Cancer Prevention Research | 2009

A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions

Susanne K. Kjaer; Kristján Sigurdsson; Ole-Erik Iversen; Mauricio Hernandez-Avila; Cosette M. Wheeler; Gonzalo Perez; Darron R. Brown; Laura A. Koutsky; Eng Tay; Patricia J. García; Kevin A. Ault; Suzanne M. Garland; Sepp Leodolter; Sven-Eric Olsson; Grace W.K. Tang; Daron G. Ferris; Jorma Paavonen; Matti Lehtinen; Marc Steben; F. Xavier Bosch; Joakim Dillner; Elmar A. Joura; Slawomir Majewski; Nubia Muñoz; Evan R. Myers; Luisa L. Villa; Frank J. Taddeo; Christine Roberts; Amha Tadesse; Janine T. Bryan

Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18–related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18–related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18–related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.


Vaccine | 2008

HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine

Elmar A. Joura; Susanne K. Kjaer; Cosette M. Wheeler; Kristján Sigurdsson; Ole Erik Iversen; Mauricio Hernandez-Avila; Gonzalo Perez; Darron R. Brown; Laura A. Koutsky; Eng Tay; Patricia J. García; Kevin A. Ault; Suzanne M. Garland; Sepp Leodolter; Sven Eric Olsson; Grace W.K. Tang; Daron G. Ferris; Jorma Paavonen; Matti Lehtinen; Marc Steben; Xavier Bosch; Joakim Dillner; Robert J. Kurman; Slawomir Majewski; Nubia Muñoz; Evan R. Myers; Luisa L. Villa; Frank J. Taddeo; Christine Roberts; Amha Tadesse

The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers.


Human Vaccines | 2009

Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

Sven Eric Olsson; Susanne K. Kjaer; Kristján Sigurdsson; Ole Erik Iversen; Mauricio Hernandez-Avila; Cosette M. Wheeler; Gonzalo Perez; Darron R. Brown; Laura A. Koutsky; Eng Tay; Patricia J. García; Kevin A. Ault; Suzanne M. Garland; Sepp Leodolter; Grace W.K. Tang; Daron G. Ferris; Jorma Paavonen; Matti Lehtinen; Marc Steben; F. Xavier Bosch; Joakim Dillner; Elmar A. Joura; Slawomir Majewski; Nubia Muñoz; Evan R. Myers; Luisa L. Villa; Frank J. Taddeo; Christine Roberts; Amha Tadesse; Janine T. Bryan

Objective In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Methods 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Results Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment. Conclusions These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.


The Journal of Infectious Diseases | 1997

Human papillomavirus type 11 (HPV-11) neutralizing antibodies in the serum and genital mucosal secretions of African green monkeys immunized with HPV-11 virus-like particles expressed in yeast.

Robert S. Lowe; Darron R. Brown; Janine T. Bryan; James Cook; Hugh A. George; Kathryn J. Hofmann; William Hurni; Joseph G. Joyce; E. Dale Lehman; Henry Z. Markus; Michael P. Neeper; Loren D. Schultz; Alan R. Shaw; Kathrin U. Jansen

It has been shown previously that immunization of animals with recombinant virus-like particles (VLPs) consisting of the viral capsid proteins L1 or L1 plus L2 protected animals against experimental viral challenge. However, none of these experimental models addresses the issue of whether systemic immunization with VLPs elicits a neutralizing antibody response in the genital mucosa. Such a response may be necessary to protect the uterine cervix against infection with genital human papillomavirus (HPV) types. African green monkeys systemically immunized with HPV-11 VLPs expressed in Saccharomyces cerevisiae and formulated on aluminum adjuvant elicited high-titered HPV-11 VLP-specific serum antibody responses. Sera from these immunized monkeys neutralized HPV-11 in the athymic mouse xenograft system. Significant levels of HPV-11-neutralizing antibodies also were observed in cervicovaginal secretions. These findings suggest that protection against HPV infection of the uterine cervix may be possible through systemic immunization with HPV VLPs.


Clinical Infectious Diseases | 2016

Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience

Suzanne M. Garland; Susanne K. Kjaer; Nubia Muñoz; Stan L. Block; Darron R. Brown; Mark J. DiNubile; Brianna Lindsay; Barbara J. Kuter; Gonzalo Perez; Géraldine Dominiak-Felden; Alfred J. Saah; Rosybel Drury; Rituparna Das; Christine Velicer

This systematic review assessed the global impact and effectiveness of quadrivalent human papillomavirus (HPV) vaccination on HPV infection and disease in real-world settings over a decade of use. Substantial reductions in HPV 6/11/16/18 infection, anogenital warts, and cervical lesions have been achieved.


Human Vaccines | 2007

Antibodies from Women Immunized with Gardasil ® Cross-Neutralize HPV 45 Pseudovirions

Judith F. Smith; Michelle K. Brownlow; Martha Brown; Rose Kowalski; Mark T. Esser; Wanda Ruiz; Eliav Barr; Darron R. Brown; Janine T. Bryan

Human papillomavirus (HPV) types 6, 11, 16 and 18 L1 virus-like particles (VLPs) have been used to generate the prophylactic quadrivalent vaccine, Gardasil®. There is a high degree of homology within the L1 major capsid protein sequence of genital HPV types and it is therefore likely that there is a substantial degree of antigenic similarity of the surface exposed epitopes on the virion particles or on VLPs. It is possible then, that antibodies induced by immunization with Gardasil® could bind, and even neutralize HPV types that are closely related to the vaccine types. An investigation of antibody binding and neutralization was undertaken focusing on two members of the A7 species, HPV 18 and HPV 45. Polyclonal sera from Gardasil® recipients and from HPV 18 L1 VLP recipients were evaluated. Utilizing the pseudovirus neutralization assay developed by the National Cancer Institute, antibodies induced by the vaccines were found to cross-neutralize HPV 45 pseudovirions (PsV). Examination of a panel of monoclonal antibodies made against L1 VLPs revealed the presence of conformational, neutralizing epitopes on the surface of VLPs that may be shared between HPV 18 and HPV 45. These data demonstrate that Gardasil® immunization induces antibodies capable of neutralizing HPV 18 PsV and HPV 45 PsV in vitro.

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Daron G. Ferris

Georgia Regents University

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