Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo.
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ABSTRACT:
SUBMITTER: Derby N
PROVIDER: S-EPMC6155161 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo.
Derby Nina N Lal Manjari M Aravantinou Meropi M Kizima Larisa L Barnable Patrick P Rodriguez Aixa A Lai Manshun M Wesenberg Asa A Ugaonkar Shweta S Levendosky Keith K Mizenina Olga O Kleinbeck Kyle K Lifson Jeffrey D JD Peet M Melissa MM Lloyd Zachary Z Benson Michael M Heneine Walid W O'Keefe Barry R BR Robbiani Melissa M Martinelli Elena E Grasperge Brooke B Blanchard James J Gettie Agegnehu A Teleshova Natalia N Fernández-Romero José A JA Zydowsky Thomas M TM
Nature communications 20180924 1
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. Moreover, on-demand products are currently missing from the PrEP development portfolio. Griffithsin (GRFT) is a non-antiretroviral HIV entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. When combined ...[more]
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Project description:Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p?=?0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5×10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use.
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