Preclinical evaluation of the immunomodulatory lymphocyte trafficking drug FTY720 for HIV prevention in the female genital mucosa of macaques
Monica Morris
Total Solutions, Atlanta, GA, USA
These authors contributed equally to this work.Search for more papers by this authorRachael D. Aubert
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
These authors contributed equally to this work.Search for more papers by this authorKatherine Butler
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorTara Henning
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorJames Mitchell
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorLeecresia Jenkins
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorDavid Garber
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorJanet McNicholl
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorCorresponding Author
Ellen N. Kersh
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Correspondence
Ellen Kersh, Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control
1600 Clifton Rd NE, MS A25, Bldg 17, rm 3229, Atlanta, GA 30333, USA.
Tel.: +1 404 639 2728;
Fax: +1 404 639 4233;
e-mail: [email protected]
Search for more papers by this authorMonica Morris
Total Solutions, Atlanta, GA, USA
These authors contributed equally to this work.Search for more papers by this authorRachael D. Aubert
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
These authors contributed equally to this work.Search for more papers by this authorKatherine Butler
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorTara Henning
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorJames Mitchell
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorLeecresia Jenkins
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorDavid Garber
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorJanet McNicholl
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Search for more papers by this authorCorresponding Author
Ellen N. Kersh
Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control, Atlanta, GA, USA
Correspondence
Ellen Kersh, Laboratory Branch, Division HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis STD, and TB Prevention, Centers for Disease Control
1600 Clifton Rd NE, MS A25, Bldg 17, rm 3229, Atlanta, GA 30333, USA.
Tel.: +1 404 639 2728;
Fax: +1 404 639 4233;
e-mail: [email protected]
Search for more papers by this authorAbstract
FTY720 has been shown to reduce inflammatory cytokines and immune cells in the genital mucosa of macaques. This pilot study examined the ability of FTY720 to inhibit HIV acquisition. Systemic treatment with FTY720 failed to prevent or delay vaginal SHIV transmission.
References
- 1Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P: Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discovery 2010; 9: 883–97.
- 2Cohen J: AIDS research. Microbicide fails to protect against HIV. Science 2008; 319: 1026–7.
- 3Dobard C, Sharma S, Martin A, Pau CP, Holder A, Kuklenyik Z, Lipscomb J, Hanson DL, Smith J, Novembre FJ, Garcia-Lerma JG, Heneine W: Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue. J Virol 2012; 86: 718–25.
- 4Friend DR, Kiser PF: Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned. Antiviral Res 2013; 99: 391–400.
- 5Haase AT: Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 2011; 62: 127–39.
- 6Kersh EN, Luo W, Adams DR, Mitchell J, Garcia-Lerma JG, Butera S, Folks T, Otten R: Evaluation of the lymphocyte trafficking drug FTY720 in SHIVSF162P3-infected rhesus macaques. J Antimicrob Chemother 2009; 63: 758–62.
- 7Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, Reilly CS, Peterson ML, Schultz-Darken N, Brunner KG, Nephew KR, Pambuccian S, Lifson JD, Carlis JV, Haase AT: Glycerol monolaurate prevents mucosal SIV transmission. Nature 2009; 458: 1034–8.
- 8Ma Z, Lu FX, Torten M, Miller CJ: The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques. Clin Immunol 2001; 100: 240–9.
- 9Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG: Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004; 427: 355–60.
- 10Murooka TT, Deruaz M, Marangoni F, Vrbanac VD, Seung E, von Andrian UH, Tager AM, Luster AD, Mempel TR: HIV-infected T cells are migratory vehicles for viral dissemination. Nature 2012; 490: 283–7.
- 11Nr C: Guide for the Care and Use of Laboratory Animals, 8th edn. Washington, DC: National Academy Press, 2011.
- 12Pudney J, Quayle AJ, Anderson DJ: Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone. Biol Reprod 2005; 73: 1253–63.
- 13Radzio J, Aung W, Holder A, Martin A, Sweeney E, Mitchell J, Bachman S, Pau CP, Heneine W, Garcia-Lerma JG: Prevention of vaginal SHIV transmission in macaques by a coitally-dependent Truvada regimen. PLoS ONE 2012; 7: e50632.
- 14Subbarao S, Otten RA, Ramos A, Kim C, Jackson E, Monsour M, Adams DR, Bashirian S, Johnson J, Soriano V, Rendon A, Hudgens MG, Butera S, Janssen R, Paxton L, Greenberg AE, Folks TM: Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges. J Infect Dis 2006; 194: 904–11.
- 15Tsuiki A, Luo W, Henning T, Vishwanathan S, Dinh C, Adams D, Sweeney E, Mitchell J, Bachman S, Sharma P, Powell N, Hendry M, McNicholl J, Kersh E: Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues. J Med Primatol 2013; 42: 89–100.
