title: In vitro and in vivo evaluation of two carrageenan-based formulations to prevent HPV acquisition.
abstract: Commercial vaccines against human papillomavirus (HPV) have low uptake due to parental autonomy, dosing regimen, cost, and cold chain storage requirements. Carrageenan (CG)-based formulations prevent HPV infection in vitro and in vivo but data are needed on the durability of anti-HPV activity and the effect of seminal plasma (SP). The Population Council's PC-515 gel and the lubricant Divine 9 were tested for their physicochemical properties and anti-HPV activity against HPV16, 18, and 45 pseudoviruses (PsVs). Anti-PsV activity was estimated using the luciferase assay in HeLa cells and the HPV PsV luciferase mouse model. Formulations were applied intravaginally either 2h pre/2h post (-2h/+2h) or 24h pre (-24h) relative to challenge with HPV16 or 45 PsV in PBS or SP/PBS. Both formulations showed broad-spectrum anti-HPV activity in vitro (IC50: 1-20ng/ml), significantly decreasing HPV PsV infection in the mouse model (-2h/+2h, p<0.0001). PC-515 protected better than Divine 9 in the -24h dosing regimen (p<0.0001) and comparable to Divine 9 in the -2h/+2h regimen (p=0.9841). PC-515 retained full activity in the murine model when PsV solutions contained human SP. The durable, potential broad-spectrum anti-HPV activity of CG formulations in the presence of SP supports their further development to prevent HPV acquisition.
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Aixa
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Kleinbeck
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Mizenina
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kizima
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Levendosky
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Ninochka
authors.initials: N
authors.lastname: Jean-Pierre
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Villegas
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Ford
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cooney
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
authors.affiliation: The Population Council, New York, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zydowsky
authors.affiliation: The Population Council, New York, NY, USA. Electronic address: jromero@popcouncil.org.
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández Romero
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002351:Carrageenan / Q000494:pharmacology* / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D027383:Papillomaviridae / Q000187:drug effects*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D056990:Post-Exposure Prophylaxis / Q000379:methods; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D012661:Semen / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D002351:Carrageenan; D008156:Luciferases
keywords: HPV; Microbicides; STI