In Vitro and In Vivo Testing of Microbicides
Council research is advancing microbicide strategies to prevent dendritic cell–driven infection of HIV across the body surfaces.
Human immunodeficiency virus (HIV) is frequently acquired sexually; the virus crosses the genital/rectal/oral surfaces to enter the body and establish infection. Increasingly, research is exploring how agents called microbicides can be applied prior to or after sexual activity to limit infection.
Council research spans testing specific agents that target unique molecules on the surface of the cells or the virus that are critical for HIV infection, as well as Carraguard®-based approaches—that is, broad-acting products that prevent virus–cell contact, independent of the molecules involved. This research is being conducted in collaboration with Council researchers Thomas Zydowsky and Jose Fernandez-Romero.
Dendritic cells (a type of white blood cell) play a major role in HIV transmission. Council research is exploring how virus capture by and infection of dendritic cells can be limited by candidate microbicides. In addition, Council researchers are testing whether microbicides can prevent the spread of virus from dendritic cells to CD4 T cells. In vitro studies focus specifically on analyzing the use of small molecules to inhibit virus attachment, entry, and fusion for the prevention of dendritic cell–driven infection at the mucosa. Research continues to optimize the effectiveness of these blocking agents (alone and in combination) to identify novel approaches that are tested in vivo in collaboration with John Moore and Robin Shattock. In vivo studies currently being carried out at the Population Council are yielding promising proof-of-principle results for the ability of Carraguard-based microbicides to prevent sexual transmission of HIV even in the presence of other sexually transmitted infections.
New-generation microbicides (new gel formulations, vaginal rings, and agents that act rectally) also are being pursued through in vitro and in vivo testing.
See also: Robbiani laboratory
A fusion inhibitor prevents spread of immunodeficiency viruses, but not activation of virus-specific T cells, by dendritic cells (abstract) (PDF) (HTML)
Frank,Ines; Stoessel,Hella; Gettie,Agegnehu; Turville,Stuart G.; Bess Jr.,Julian W.; Lifson,Jeffrey D.; Sivin,Irving; Romani,Nikolaus; Robbiani,Melissa
Journal of Virology 82(11): 5329-5339
Publication date: 2008
CD4-specific Designed Ankyrin Repeat Proteins are novel potent HIV entry inhibitors with unique characteristics (abstract) (PDF)
Schweizer,Andreas; Rusert,Peter; Berlinger,Livia; Ruprecht,Claudia R.; Mann,Axel; Corthesy,Stephanie; Turville,Stuart G.; Aravantinou,Meropi; Fischer,Marek; Robbiani,Melissa; Amstutz,Patrick; Trkola,Alexandra
PLoS Pathogens 4(7): e1000109-
Publication date: 2008
Efficacy of Carraguard-based microbicides in vivo despite variable in vitro activity (abstract) (PDF)
Turville,Stuart G.; Aravantinou,Meropi; Miller,Todd; Kenney,Jessica; Teitelbaum,Aaron; Hu,Lieyu; Chudolij,Anne; Zydowsky,Thomas M.; Piatak Jr.,Michael; Bess Jr.,Julian W.; Lifson,Jeffrey D.; Blanchard,James; Gettie,Agegnehu; Robbiani,Melissa
PLoS ONE 3(9): e3162-
Publication date: 2008
Resolution of de novo
HIV production and trafficking in immature dendritic cells (abstract) (HTML)
Turville,Stuart G.; Aravantinou,Meropi; Stoessel,Hella; Romani,Nikolaus; Robbiani,Melissa
Nature Methods 5(1): 75-85
Publication date: 2008
Carrageenan/MIV-150 (PC-815), a combination microbicide (abstract) (HTML)
Fernandez-Romero,Jose A.; Thorn,Mitchell; Turville,Stuart G.; Titchen,Kanani; Sudol,Kristin M.; Li,Jifan; Miller,Todd; Robbiani,Melissa; Maguire,Robin A.; Buckheit Jr.,Robert W.; Hartman,Tracy L.; Phillips,David M.
Sexually Transmitted Diseases 34(1): 9-14
Publication date: 2007
Current concepts of HIV transmission (abstract) (HTML)
Morrow,Gavin; Vachot,Laurence; Vagenas,Panagiotis; Robbiani,Melissa
Current HIV/AIDS Reports 4(1): 29-35
Publication date: 2007
Lymphocyte-dendritic cell interactions and mucosal acquisition of SIV/HIV infection (abstract) (HTML)
Turville,Stuart G.; Peretti,Silvia; Pope,Melissa
Current Opinion in HIV and AIDS 1(1): 3-9
Publication date: 2006
Slamming the door on unwanted guests: Why preemptive strikes at the mucosa may be the best strategy against HIV (abstract) (PDF)
Trapp,Susanna; Turville,Stuart G.; Robbiani,Melissa
Journal of Leukocyte Biology 80(5): 1076-1083
Publication date: 2006
Elimination of retroviral infectivity by N-ethylmaleimide with preservation of functional envelope glycoproteins (abstract) (HTML)
Morcock,David R.; Thomas,James A.; Gagliardi,Tracy D.; Gorelick,Robert J.; Roser,J.David; Chertova,Elena N.; Bess Jr.,Julian W.; Ott,David E.; Sattentau,Quentin J.; Frank,Ines; Pope,Melissa; Lifson,Jeffrey D.; Henderson,Louis E.; Crise,Bruce J.
Journal of Virology 79(3): 1533-1542
Publication date: 2005
Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses (abstract) (PDF) (HTML)
Peretti,Silvia; Shaw,Andrew; Blanchard,James; Bohm,Rudolf; Morrow,Gavin; Lifson,Jeffrey D.; Gettie,Agegnehu; Pope,Melissa
Blood 106(4): 1305-1313
Publication date: 2005
Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue (abstract) (PDF) (HTML)
Hu,Qinxue; Frank,Ines; Williams,Vennansha G.; Santos,John J.; Watts,Patricia; Griffin,George E.; Moore,John P.; Pope,Melissa; Shattock,Robin J.
Journal of Experimental Medicine 199(8): 1065-1075
Publication date: 2004
Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells (abstract) (PDF) (HTML)
Turville,Stuart G.; Santos,John J.; Frank,Ines; Cameron,Paul U.; Wilkinson,John; Miranda-Saksena,Monica; Dable,Joanne; Stoessel,Hella; Romani,Nikolaus; Piatak Jr.,Michael; Lifson,Jeffrey D.; Pope,Melissa; Cunningham,Anthony L.
Blood 103(6): 2170-2179
Publication date: 2004
Entry inhibitors SCH-C, RANTES, and T-20 block HIV type 1 replication in multiple cell types (abstract) (HTML)
Ketas,Thomas J.; Klasse,Per Johan; Spenlehauer,Catherine; Nesin,Mirjana; Frank,Ines; Pope,Melissa; Strizki,Julie M.; Reyes,Gregory R.; Baroudy,Bahige M.; Moore,John P.
AIDS Research and Human Retroviruses 19(3): 177-186
Publication date: 2003
Human immunodeficiency virus type 1 attachment, coreceptor, and fusion inhibitors are active against both direct and trans infection of primary cells (abstract) (PDF) (HTML)
Ketas,Thomas J.; Frank,Ines; Klasse,Per Johan; Sullivan,Brian M.; Gardener,Jason P.; Spenlehauer,Catherine; Nesin,Mirjana; Olson,William C.; Moore,John P.; Pope,Melissa
Journal of Virology 77(4): 2762-2767
Publication date: 2003
Immunodeficiency virus exploitation of dendritic cells in the early steps of infection (abstract) (PDF) (HTML)
Teleshova,Natalia; Frank,Ines; Pope,Melissa
Journal of Leukocyte Biology 74(5): 683-690
Publication date: 2003
Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120 (abstract) (HTML)
Veazey,Ronald S.; Shattock,Robin J.; Pope,Melissa; Kirijan,J.Christian; Jones,Jennifer; Hu,Qinxue; Ketas,Thomas J.; Marx,Preston A.; Klasse,Per Johan; Burton,Dennis R.; Moore,John P.
Nature Medicine 9(3): 343-346
Publication date: 2003
Transmission, acute HIV-1 infection and the quest for strategies to prevent infection (abstract) (HTML)
Pope,Melissa; Haase,Ashley T.
Nature Medicine 9(7): 847-852
Publication date: 2003
Project Stats
Location: United States
Program(s):
HIV and AIDS
Topic(s):
HIV biomedical research
Duration: 1/2005 - ongoing
Population Council researchers:
Meropi Aravantinou
Nina Derby
Ines Frank
Joselin Galvez
Jessica Kenney
Elena Martinelli
Melissa Robbiani
Loreley Villamide-Herrera
Non-Council collaborators:
Agegnehu Gettie (Aaron Diamond AIDS Research Center)
James Blanchard (Tulane National Primate Research Center)
Jeffrey Lifson (National Cancer Institute)
Michael Piatak (National Cancer Institute)
Donors:
Swedish International Development Cooperation Agency
Swedish Ministry for Foreign Affairs
US Agency for International Development
US National Institutes of Health
Get Involved
- Make a contribution to the Population Council
- Honor a loved one with a gift in his or her name
- Sign up to receive e-mail announcements
Connect
