Publication of Clinical Trial Results

Politch JA, Cu-Uvin S, Moench TR, Tashima KT, Marathe JG, Guthrie KM, Cabral H, Nyhuis T, Brennan M, Zeitlin L, Spiegel HML, Mayer KH, Whaley KJ, Anderson DJ. Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66):  A Phase I randomized trial. PLoS Med, 2021;18(2):e1003495.


IPCP Investigators:

Journal of Infectious Diseases Supplement:  Cell-Associated HIV Transmission Across Mucosal Surfaces:

1.         Anderson DJ, Le Grand R. Cell-associated HIV mucosal transmission: the neglected pathway.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S606-8. doi: 10.1093/infdis/jiu538.

2.         Politch JA, Marathe J, Anderson DJ. Characteristics and quantities of HIV host cells in human genital tract secretionsJ Infect Dis. 2014 Dec 15;210 Suppl 3:S609-15. doi: 10.1093/infdis/jiu390. Review.

3.         Cone RA. Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIVJ Infect Dis. 2014 Dec 15;210 Suppl 3:S616-21. doi: 10.1093/infdis/jiu459. Review.

4.         Gummuluru S, Pina Ramirez NG, Akiyama H.  CD169-dependent cell-associated HIV-1 transmission: a driver of virus dissemination.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S641-7. doi: 10.1093/infdis/jiu442. Review.

5.         Anderson DJ.  Modeling mucosal cell-associated HIV type 1 transmission in vitro.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S648-53. doi: 10.1093/infdis/jiu537. Review.

6.         Moench TR.  Cell-associated transmission of HIV type 1 and other lentiviruses in small-animal models.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S654-9. doi: 10.1093/infdis/jiu368. Review.

7.         Sagar M.  Origin of the transmitted virus in HIV infection: infected cells versus cell-free virus.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S667-73. doi: 10.1093/infdis/jiu369. Review.

8.         Whaley KJ, Mayer KH.  Strategies for preventing mucosal cell-associated HIV transmission.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S674-80. doi: 10.1093/infdis/jiu398. Review.

Original and Review Articles:

1.         Daggett GJ Jr, Zhao C, Connor-Stroud F, Oviedo-Moreno P, Moon H, Cho MW, Moench T, Anderson DJ, Villinger F. Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.  J Med Primatol. 2017 May 9. doi: 10.1111/jmp.12264. [Epub ahead of print]

2.         Zhao C, Gunawardana M, Villinger F, Baum MM, Remedios-Chan M, Moench TR, Zeitlin L, Whaley KJ, Bohorov O, Smith TJ, Anderson DJ. Moss JA. Pharmacokinetics and preliminary safety of pod-intravaginal rings delivering the monoclonal antibody VRC01-N for HIV prophylaxis in a macaque model.  Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: e02465-16. doi: 10.1128/AAC.02465-16. Print 2017 Jul.

3.         Anderson DJ, Politch JA, Zeitlin L, Hiatt A, Kadasia K, Mayer KH, Ruprecht RM, Villinger F, Whaley KJ Systemic and topical use of monoclonal antibodies to prevent the sexual transmission of HIV.  AIDS. 2017 Jul 17;31(11):1505-1517. doi: 10.1097/QAD.0000000000001521.

4.         Guthrie KM, Rohan L, Rosen RK, Vargas SE, Shaw JG, Katz D, Kojic EM, Ham AS, Friend D, Buckheit KW, Buckheit RW Jr.  Vaginal film for prevention of HIV: using visual and tactile evaluations among potential users to inform product design.  Pharm Dev Technol. 2017 Jun 21:1-4. doi: 10.1080/10837450.2017.1339085. [Epub ahead of print]

5.         Henry CE, Wang YY, Yang Q, Hoang T, Chattopadhyay S, Hoen T, Ensign LM, Nunn KL, Schroeder H, McCallen J, Moench T, Cone R, Roffler SR, Lai SK. Anti-PEG antibodies alter the mobility and biodistribution of densely PEGylated nanoparticles in mucus. Acta Biomater. 2016 Oct 1;43:61-70. doi: 10.1016/j.actbio.2016.07.019. Epub 2016 Jul 14.

6.         Ayehunie S, Islam A, Cannon C, Landry T, Pudney J, Klausner M, Anderson DJCharacterization of a Hormone-Responsive Organotypic Human Vaginal Tissue Model: Morphologic and Immunologic Effects.  Reprod Sci. 2015 Feb 11. pii: 1933719115570906. [Epub ahead of print]

7.         Chen A, McKinley SA, Shi F, Wang S, Mucha PJ, Harit D, Forest MG, Lai SK. Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A.  PLoS One. 2015 Jul 1;10(7):e0131351. doi: 10.1371/journal.pone.0131351. eCollection 2015.

8.        Nunn KL, Wang YY, Harit D, Humphrys MS, Ma B, Cone R, Ravel J, Lai SK. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. MBio. 2015 Oct 6;6(5):e01084-15. doi: 10.1128/mBio.01084-15.

9.         Santangelo PJ, Rogers KA, Zurla C, Blanchard EL, Gumber S, Strait K, Connor-Stroud F, Schuster DM, Amancha PK, Hong JJ, Byrareddy SN, Hoxie JA, Vidakovic B, Ansari AA, Hunter E, Villinger FWhole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques.  Nat Methods. 2015 May;12(5):427-32. doi: 10.1038/nmeth.3320. Epub 2015 Mar 9

10.       Sholukh AM, Watkins JD, Vyas HK, Gupta S, Lakhashe SK, Thorat S, Zhou M, Hemashettar G, Bachler BC, Forthal DN, Villinger F, Sattentau QJ, Weiss RA, Agatic G, Corti D, Lanzavecchia A, Heeney JL, Ruprecht RM.  Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge.  Vaccine. 2015 Apr 21;33(17):2086-95. doi: 10.1016/j.vaccine.2015.02.020. Epub 2015 Mar 11.

11.        Abdel-Motal UM, Harbison C, Han T, Pudney J, Anderson DJ, Zhu Q, Westmoreland S, Marasco WA.  Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.  Gene Ther. 2014 Sep;21(9):802-10. doi: 10.1038/gt.2014.56. Epub 2014 Jun 26.

12.       Anderson DJ, Marathe J, Pudney J.  The structure of the human vaginal stratum corneum and its role in immune defense.  Am J Reprod Immunol. 2014 Jun;71(6):618-23. doi: 10.1111/aji.12230. Epub 2014 Mar 24. Review.

13.       Chen A, McKinley SA, Wang S, Shi F, Mucha PJ, Forest MG, Lai SKTransient antibody-mucin interactions produce a dynamic molecular shield against viral invasionBiophys J. 2014 May 6;106(9):2028-36. doi: 10.1016/j.bpj.2014.02.038.

14.       McKinley SA, Chen A, Shi F, Wang S, Mucha PJ, Forest MG, Lai SKModeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa.  PLoS One. 2014 Jun 26;9(6):e100598. doi: 10.1371/journal.pone.0100598. eCollection 2014.

15.       Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP.  Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.  Nature. 2014 Oct 2;514(7520):47-53. doi: 10.1038/nature13777. Epub 2014 Aug 29.

16.       Wang YY, Kannan A, Nunn KL, Murphy MA, Subramani DB, Moench T, Cone R, Lai SK.  IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections.  Mucosal Immunol. 2014 Sep;7(5):1036-44. doi: 10.1038/mi.2013.120. Epub 2014 Feb 5.

17.       Whaley KJ, Morton J, Hume S, Hiatt E, Bratcher B, Klimyuk V, Hiatt A, Pauly M, Zeitlin L.  Emerging antibody-based products Curr Top Microbiol Immunol. 2014;375:107-26. doi: 10.1007/82_2012_240. Review.

18.      Cone RA. Vaginal microbiota and sexually transmitted infections that may influence transmission of cell-associated HIV.  J Infect Dis. 2014 Dec 15;210 Suppl 3:S616-21. doi: 10.1093/infdis/jiu459.

19.       Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza S, Moench T, Cone R, Tachedjian G.  Vaginal concentrations of lactic acid potently inactivate HIV.  J Antimicrob Chemother. 2013 Sep;68(9):2015-25. doi: 10.1093/jac/dkt156. Epub 2013 May 8.

20.       Gupta S, Gach JS, Becerra JC, Phan TB, Pudney J, Moldoveanu Z, Joseph SB, Landucci G, Supnet MJ, Ping LH, Corti D, Moldt B, Hel Z, Lanzavecchia A, Ruprecht RM, Burton DR, Mestecky J, Anderson DJ, Forthal DN.  The Neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells.  PLoS Pathog. 2013;9(11):e1003776. doi: 10.1371/journal.ppat.1003776. Epub 2013 Nov 21.

21.        Harrison PF, Hemmerling A, Romano J, Whaley KJ, Young Holt B.  Developing multipurpose reproductive health technologies: an integrated strategyAIDS Res Treat. 2013;2013:790154. doi: 10.1155/2013/790154. Epub 2013 Feb 28.

22.        Hiatt A, Zeitlin L, Whaley KJ.  Multiantibody strategies for HIV.  Clin Dev Immunol. 2013;2013:632893. doi: 10.1155/2013/632893. Epub 2013 Jun 6. Review.

23.        O’Hanlon DE, Moench TR, Cone RA Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiotaPLoS One. 2013 Nov 6;8(11):e80074. doi: 10.1371/journal.pone.0080074. eCollection 2013.

24.        Whaley KJ, Zeitlin L.  Antibody-based concepts for multipurpose prevention technologiesAntiviral Res. 2013 Dec;100 Suppl:S48-53. doi: 10.1016/j.antiviral.2013.09.027. Epub 2013 Nov 1. Review.

25.        Abdel-Motal UM, Sarkis PT, Han T, Pudney J, Anderson DJ, Zhu Q, Marasco WA. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.  PLoS One 2011,6:e26473.

26.        Blaskewicz CD, Pudney J, Anderson DJ.  Structure and function of intercellular junctions in human cervical and vaginal mucosal epithelia.  Biol Reprod. 2011 Jul;85(1):97-104. doi: 10.1095/biolreprod.110.090423. Epub 2011 Apr 6.

27.        Anderson DJ, Politch JA, Nadolski AM, Blaskewicz CD, Pudney J, Mayer KH.  Targeting Trojan Horse leukocytes for HIV prevention.  AIDS. 2010 Jan 16;24(2):163-87. doi: 10.1097/QAD.0b013e32833424c8. Review.

28.        Anderson DJ, Pudney J, Schust DJ.  Caveats associated with the use of human cervical tissue for HIV and microbicide research.  AIDS. 2010 Jan 2;24(1):1-4. doi: 10.1097/QAD.0b013e328333acfb.

29.        Ayehunie S, Cannon C, Larosa K, Pudney J, Anderson DJ, Klausner M.  Development of an in vitro alternative assay method for vaginal irritation. Toxicology. 2011 Jan 11;279(1-3):130-8. doi: 10.1016/j.tox.2010.10.001. Epub 2010 Oct 17.

30.        Whaley KJ, Hanes J, Shattock R, Cone RA, Friend DR.  Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.  Antiviral Res. 2010 Dec;88 Suppl 1:S55-66. doi: 10.1016/j.antiviral.2010.09.006.

Other Relevant Publications: 

1.         Abdel-Motal UM, Sarkis PT, Han T, Pudney J, Anderson DJ, Zhu Q, Marasco WA. Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro. PLoS One 2011,6:e26473.

2.         Abela IA, Berlinger L, Schanz M, Reynell L, Gunthard HF, Rusert P, Trkola A.  Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies.  PLoS Pathogens 2012,4:e1002634.

3.         Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D. Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 2011,481:81-84.

4.         Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ, Stapleton JT, et al. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med 2012,366:34-43.

5.         Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, Moldt B, et al. Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc Natl Acad Sci U S A 2011,108:11181-11186.

6.         Chen W, Dimitrov DS. Monoclonal Antibody-Based Candidate Therapeutics Against HIV Type 1. AIDS Res Hum Retroviruses 2011.

7.         Diskin R, Scheid JF, Marcovecchio PM, West AP, Jr., Klein F, Gao H, et al. Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science,334:1289-1293.

8.         Gilbert P, Wang M, Wrin T, Petropoulos C, Gurwith M, Sinangil F, et al.Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine. J Infect Dis 2010,202:595-605.

9.         Haigwood NL, Hirsch VM. Blocking and tackling HIV. Nat Med 2009,15:841-842.

10.       Hessell AJ, Poignard P, Hunter M, Hangartner L, Tehrani DM, Bleeker WK, et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 2009,15:951-954.

11.       Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, et al. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol 2010,84:1302-1313.

12.       Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, et al.  Broad and potent neutralization of HIV-1 by a gp41-specific human antibody.  Nature 2012,491:406-12.

13.       Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, et al.  HIV therapy by a combination of broadly neutralizing antibodies in humanized mice.  Nature 2012, in press.

14.       Li Z, Palaniyandi S, Zeng R, Tuo W, Roopenian DC, Zhu X. Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection. Proc Natl Acad Sci U S A 2011,108:4388-4393.

15.       Malbec M, Porrot F, Rua R, Horwitz J, Klein F, Halper-Stromberg A, Scheid JF, Eden C, Mouquet H, Nussenzweig MC, Schwartz O.  Broadly neutralizing antibodies that inhibit HIV-1 cell to cell transmission.  J Exp Med 2013 [Epub ahead of print]

16.       McGhee JR. A mucosal gateway for vaccines. Nat Biotechnol 2011,29:136-138.

17.       NIH News.  NIH-led scientists find antibodies that prevent most HIV strains from infecting human cells.  Bethesda:  NIAID, NIH:  2010.

18.       Owen DH, Katz DF.  A vaginal fluid simulant.  Contraception  1999,59:91-5.

19.       PATH and the Coalition Advancing Multipurpose Innovations.  Saving Lives with Multipurpose Prevention Technologies:  Turning Ideas into Solutions for Sexual and Reproductive Health. Seattle: 2010.

20.       Pejchal R, Doores KJ, Walker LM, Khayat R, Huang PS, Wang SK, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 2011,334:1097-1103.

21.       Pejchal R, Walker LM, Stanfield RL, Phogat SK, Koff WC, Poignard P, et al.  Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1.  Proc Natl Acad Sci USA 2010,107:11483-8.

22.       Stamatatos L, Morris L, Burton DR, Mascola JR. Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med 2009,15:866-870.

23.       Veselinovic M, Neff CP, Mulder LR, Akkina R.  Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model.  Virology 2012,432:505-510.

24.       Voronin Y, Mofenson LM, Cunningham CK, Fowler MG, Kaleebu P, McFarland EJ, Safrit JT, Graham BS, Snow W.  HIV monoclonal antibodies: a new opportunity to further reduce mother-to-child HIV transmission.  PLoS Med. 2014 Apr 8;11(4):e1001616. doi: 10.1371/journal.pmed.1001616. eCollection 2014 Apr.

25.       Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 2011,477:466-470.

26.       Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009,326:285-289.

27.       West AP, Galimidi RP, Gnanapragasam PNP, Bjorkman PJ.  Single-chain Fv-based anti-HIV proteins:  potential and limitations.  J Virol  2012,86:195-202.

28.       Whaley KJ, Morton J, Hume S, Hiatt E, Bratcher B, Klimyuk V, Hiatt A, Pauly M, Zeitlin L.  Emerging antibody-based products.  Curr Top Microbiol Immunol 2012,Jul 8. [Epub ahead of print]

29.       Wu X, Wang C, O’Dell S, Li Y, Keele BF, Yang Z, Imamichi H, Doria-Rose N, Hoxie JA, Connors M, Shaw GM, Wyatt RT, Mascola JR.  Selection pressure on HIV-1 envelope by broadly neutralizing antibodies to the conserved CD4-binding site.  J Virol 2012,86:5844-56.

30.       Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010,329:856-861.

31.       Ye L, Zeng R, Bai Y, Roopenian DC, Zhu X. Efficient mucosal vaccination mediated by the neonatal Fc receptor. Nat Biotechnol 2011,29:158-163.

32.       Zhang MY, Borges AR, Ptak RG, Wang Y, Dimitrov AS, Alam SM, et al. Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1. MAbs 2010,2:266-274.

33.       Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010,329:811-817.