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Generation of a Dual-Target, Safe, Inexpensive Microbicide that Protects Against HIV-1 and HSV-2 Disease.

Generation of a Dual-Target, Safe, Inexpensive Microbicide that Protects Against HIV-1 and HSV-2 Disease.
Author Information (click to view)

Farr Zuend C, Nomellini JF, Smit J, Horwitz MS,


Farr Zuend C, Nomellini JF, Smit J, Horwitz MS, (click to view)

Farr Zuend C, Nomellini JF, Smit J, Horwitz MS,

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Scientific reports 2018 02 128(1) 2786 doi 10.1038/s41598-018-21134-1

Abstract

HSV-2 infection is a significant health problem and a major co-morbidity factor for HIV-1 acquisition, increasing risk of infection 2-4 fold. Condom based prevention strategies for HSV-2 and HIV-1 have not been effective at stopping the HIV-1 pandemic, indicating that alternative prevention strategies need to be investigated. We have previously developed an inexpensive HIV-1 specific microbicide that utilizes the S-layer mediated display capabilities of Caulobacter crescentus, and have shown that recombinant C. crescentus displaying HIV entry blocking proteins are able to provide significant protection from HIV-1 infection in vitro. Here we demonstrate that recombinant C. crescentus are safe for topical application and describe 5 new recombinant C. crescentus that provide protection from HIV-1 infection in vitro. Further, we demonstrate protection from disease following intravaginal infection with HSV-2 in a murine model using C. crescentus expressing the anti-viral lectins Cyanovirin-N and Griffithsin, as well as α-1-antitrypsin and indolicidin. Interestingly, C. crescentus alone significantly reduced HSV-2 replication in vaginal lavage fluid. Protection from HSV-2 disease was strongly associated with early cytokine production in the vaginal tract. Our data support the potential for a dual-target microbicide that can protect against both HIV-1 and HSV-2, which could have an enormous impact on public health.

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