Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010

Brinckmann, Sarah; Costa, Kelly Da; Gils, Marit J. van; Holzmann, David; Klein, Katja; Madeira, Luisa; Mainetti, Lara; Raue, Katharina; Reinhart, David; Reudelsterz, Marc; Ruffin, Nicolas; Seifried, Janna; Schäfer, Katrein; Sheik-Khalil, Enas; Sköld, Annette E.; Uchtenhagen, Hannes; Vabret, Nicolas; Ziglio, Serena; Scarlatti, Gabriella; Shattock, Robin J.; Wahrén, Britta; Gotch, Frances

doi:10.1186/1479-5876-9-40

Cited by 11 publications

(11 citation statements)

References 44 publications

(48 reference statements)

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“…A number of non-ARV formulations are currently in preclinical or clinical testing (5): VivaGel (SPL7013 dendrimer) (52), Praneen (Polyherbal tablet) (53), Griffithsin (GRFT red algal lectin) (54,55), aptamers (56,57), and Mabgel (monoclonal antibodies) (58). ZA/CG, like most of the non-ARV candidates mentioned above, is a safe, nearly iso-osmolal formulation with proven activity against HIV.…”

Section: Discussionmentioning

confidence: 99%

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

Kenney

Rodríguez

Kizima

et al. 2013

Antimicrob Agents Chemother

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We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P ‫؍‬ 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P ‫؍‬ 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2. S everal recent clinical trials have shown that microbicides containing antiretroviral drugs (ARVs) reduce the sexual transmission of HIV and other sexually transmitted diseases (STIs) (1). The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial (CAPRISA-004) showed that pericoital use (before and after sex) of vaginally applied 1% tenofovir (TFV) gel reduced human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2) acquisition by 39% and 51%, respectively (2). Similarly, three oral pre-exposure trials (iPrex, Partners PrEP, and TDF2) targeting men who have sex with men (MSM) and transgender women, HIV-serodiscordant couples, or heterosexual men and women demonstrated between 44% and 73% efficacy (1). Conversely, a lack of efficacy was seen in two trials (FEM-PrEP and VOICE) in which women received daily oral emtricitabine-TFV and TFV (1, 3). A recent analysis of these two studies suggested that the lack of efficacy could have been due to poor regimen adherence (1, 3, 4).Although ARV-containing topical microbicides will likely be available soon, there are important questions regarding their use. (i) Does topical administration of an ARV in people with an undiagnosed HIV infection lead to resistance development and affect their treatment outcomes? (ii) How accessible will these products be (i.e., will they be available over the counter or by prescription only)? (iii) Can the introduction of an HIV-specific microbicide increase the transmission of other STIs?Given these unanswered questions and the potential limitations of ARV-containing topical microbicides, we are ...

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Section: Discussionmentioning

confidence: 99%

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

Kenney

Rodríguez

Kizima

et al. 2013

Antimicrob Agents Chemother

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“…Indeed, the vaginal and cervical epithelium have been shown to be transiently infectable by HIV-1 and most likely play a role in transporting the virus to target local T cells, resulting in productive systemic viral infection [6,30,31]. This is also the surface targeted for microbicide therapeutics [32][33][34][35][36].…”

Section: Fsl-gb 3 Inhibits Hiv-1 Iiib Infection Of Human Endometrial mentioning

confidence: 97%

“…Condoms are an excellent way to prevent infection; however, in many countries where the HIV incidence is high, men are reluctant to use them [5]. There has thus been renewed interest in new prevention strategies, and in particular, in the development of topical agents or 'microbicides' for vaginal and/ or rectal mucosal use for the purpose of preventing HIV transmission [5][6][7][8][9][10]. Unfortunately, use of microbicides for prevention of anal transmission of HIV has not been adequately addressed as yet.…”

mentioning

confidence: 97%

A Novel VSV/HIV Pseudotype Approach for the Study of HIV Microbicides Without Requirement for level 3 Biocontainment

Harrison

Henry

Mahfoud³

et al. 2011

Future Virol.

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Studies of potential HIV mucosal microbicides are difficult to undertake due to the requirement for a suitable animal model and the use of biosafety level 3 containment, which are not always available to researchers. Here we show the use of a mouse model of vaginal and rectal transmission of an HIV chimeric virus that does not require level 3 biosafety containment, to test the ex vivo efficacy of soluble Gb3 analogs for the prevention of mucosal HIV infection. The model uses a pseudoenvelope-typed vesicular stomatitis virus (VSV)/HIV recombinant virus that can infect all murine cell types. We demonstrate that the envelope glycoproteins VSV-G of VSV and gp-120 of HIV both bind Gb3. We show that soluble Gb3 analogs inhibit in vitro infection of cervical and vaginal-derived cell lines by both intact HIV and the VSV/HIV recombinant virus. Soluble Gb3 analogs incorporated into gel or used alone and applied directly to the vaginal and rectal mucosal tissue of mice were able to resist viral infection as monitored by PCR and quantitative real-time PCR copy number of HIV cDNA extracted from mouse tissue. Only a trend towards significant efficacy for prevention of mucosal transmission through lower copy number in the treatment groups was evident from these studies; however, this finding warrants further evaluation. In addition, we illustrate a methodology to evaluate inflammatory responses in either vagina or rectum after administration of soluble microbicidal compounds. These studies provide a potential new ex vivo methodology suitable for animal facilities in general, to screen microbicide drug candidates, including drug candidates that target viral proteins, for efficacy and safety, in order to accelerate development and discovery of prophylactic and therapeutic agents for HIV/AIDS.

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“…Scientific data from earlier meetings were summarized previously [1,2]. New important data from oral and poster presentations were discussed by all collaborators at the conference and are summarised here by our PhD students.…”

Section: Introductionmentioning

confidence: 99%

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

et al. 2012

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Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

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Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010

Cited by 11 publications

References 44 publications

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection In Vivo

A Novel VSV/HIV Pseudotype Approach for the Study of HIV Microbicides Without Requirement for level 3 Biocontainment

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

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