lipid-a and Condylomata-Acuminata

Vaccines are available against human papillomavirus (HPV), the causal agent of cervical and other cancers. Efficacy data from the HPV-16/18 AS04-adjuvanted vaccine clinical trial program were reviewed. Six randomized, controlled phase II/III trials evaluating cervical endpoints enrolled women from diverse populations and geographical locations. The program analyzed extensively the cohorts most relevant from a public health perspective: the total vaccinated cohort (TVC), approximating a general population including those with existing or previous HPV infection, and TVC-naïve, approximating a population of young women before sexual debut. Results show that the vaccine reduces HPV-16/18 infection and associated cervical endpoints in women regardless of age, location, or sexual experience. It provides cross-protection against some non-vaccine oncogenic HPV types and types causing genital warts, and may be effective against vulvar, oral, and anal HPV infection. Early epidemiology data following its introduction suggest a decline in the prevalence of vaccine and some non-vaccine HPV types.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Anus Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Condylomata Acuminata; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Lipid A; Mouth Neoplasms; Papillomavirus Infections; Papillomavirus Vaccines; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms

Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts.. A total of 457 subjects with anogenital warts were screened, of which 320 with HPV-6 and/or HPV-11 infection were enrolled into 2 double-blind, placebo-controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin.. Although a positive trend toward clearance was seen in patients infected with only HPV-6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV-6 and/or HPV-11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects.. Infection with multiple HPV types, including high-risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Capsid Proteins; Condylomata Acuminata; DNA, Viral; Double-Blind Method; Drug Combinations; Female; Genotype; Human papillomavirus 6; Humans; Lipid A; Male; Middle Aged; Oncogene Proteins, Viral; Papillomaviridae; Papillomavirus Vaccines; Placebos; Podophyllotoxin; Polymerase Chain Reaction; Saponins; Vaccines, Synthetic; Viral Vaccines

Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent.. Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations.. In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74.. The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Clinical Trials, Phase III as Topic; Condylomata Acuminata; Double-Blind Method; Female; Human papillomavirus 16; Human papillomavirus 18; Human papillomavirus 6; Humans; Incidence; Incidental Findings; Lipid A; Multicenter Studies as Topic; Papillomavirus Vaccines; Randomized Controlled Trials as Topic; Treatment Outcome; Vaccination

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.

Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Animals; Antigens, Viral; Condylomata Acuminata; Humans; Interferon-gamma; Lipid A; Male; Mice; Mice, Inbred CBA; Oncogene Proteins, Viral; Rabbits; Recombinant Fusion Proteins; Viral Structural Proteins; Viral Vaccines