AIDS

Animal Models

  • SIV/SHIV rhesus macaque model
  • HIV/humanized mouse models

Study Types

  • Vaccine testing
  • Therapeutics testing
  • PK/safety testing
  • Pathogenesis

In vitro Services

  • Sample processing
  • CD4/8 cell counts
  • QT-PCR viral load testing
  • Binding antibody ELISA
  • Functional T cell assays

Representative Publications

Neonatal immunity associated with heterologous HIV-1 neutralizing antibody induction in SHIV-infected Rhesus Macaques
Holmes S, Li H, Shen X, Martin M, Tuck R, Chen Y, Giorgi EE, Kirshner HF, Berry M, Van Italie E, Venkatayogi S, Martin Beem JS, Edwards RJ, Mansouri K, Singh A, Kuykendall C, Gurley T, Anthony Moody M, DeNayer N, Demarco T, Denny TN, Wang Y, Evangelous TD, Clinton JT, Hora B, Wagh K, Seaman MS, Saunders KO, Solomotis N, Misamore J, Lewis MG, Wiehe K, Montefiori DC, Shaw GM, Williams WB.
Nat Commun. 2024 Nov 27;15(1):10302. doi: 10.1038/s41467-024-54753-6.
PMID: 39604409

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs

Mu Z, Whitley J, Martik D, Sutherland L, Newman A, Barr M, Parks R, Wiehe K, Cain DW, Hodges KZ, Venkatayogi S, Lee EM, Smith L, Mansouri K, Edwards RJ, Wang Y, Rountree W, Alameh M-G, Tam Y, Barbosa C, Tomai M, Lewis MG, Santrai S, Maughan M, Tian M, Alt FW, Weissman D, Saunders KO, Haynes BF.
J Virol. 2024 Aug 13:e0013724. doi: 10.1128/jvi.00137-24. Online ahead of print.
PMID: 39136461

Arenavirus-Based Vectors Generate Robust SIV Immunity in Non-Human Primates.

Sharma B, Bekerman E, Truong H, Lee J, Gamez-Guerrero M, Boopathy A, Mital R, Huang KB, Ahmadi-Erber S, Wimmer R, Schulha S, Lauterbach H, Orlinger K, Suthram S, Lewis MG, Blair W, Makadzange T, Geleziunas R, Murry JP, Schmidt S.
Vaccines (Basel). 2024 Jul 2;12(7):735. doi: 10.3390/vaccines12070735.
PMID: 39066373

Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques.

Saunders KO, Counts J, Thakur B, Stalls V, Edwards R, Manne K, Lu X, Mansouri K, Chen Y, Parks R, Barr M, Sutherland L, Bal J, Havill N, Chen H, Machiele E, Jamieson N, Hora B, Kopp M, Janowska K, Anasti K, Jiang C, Van Itallie E, Venkatayogi S, Eaton A, Henderson R, Barbosa C, Alam SM, Santra S, Weissman D, Moody MA, Cain DW, Tam YK, Lewis M, Williams WB, Wiehe K, Montefiori DC, Acharya P, Haynes BF.

Cell. 2024 Jan 4;187(1):79-94.e24. doi: 10.1016/j.cell.2023.12.002.

PMID:38181743

Host immunity associated with spontaneous suppression of viremia in therapy-nave young rhesus macaques following neonatal SHIV infection.

Evangelous TD, Berry M, Venkatayogi S, LeMaster C, Geanes ES, De Naeyer N, DeMarco T, Shen X, Li H, Hora B, Solomonis N, Misamore J, Lewis MG, Denny TN, Montefiori D, Shaw GM, Wiehe K, Bradley T, Williams WB.
J Virol. 2023 Oct 24:e0109423. doi: 10.1128/jvi.01094-23. Online ahead of print.
PMID:37874153

 

Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates.

Burdo TH, Chen C, Kaminski R, Sariyer IK, Mancuso P, Donadoni M, Smith MD, Sariyer R, Caocci M, Liao S, Liu H, Huo W, Zhao H, Misamore J, Lewis MG, Simonyan V, Xu EY, Cradick TJ, Gordon J, Khalili K.
Gene Ther. 2023 Aug 17. doi: 10.1038/s41434-023-00410-4. Online ahead of print.
PMID:37587230

 

Duke University and BIOQUAL researchers establishes a neonatal rhesus macaque model for studying development of heterologous HIV-1 nAbs

Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies.
Hora B, Li H, Shen X, Martin M, Chen Y, Berry M, Evangelous T, Macintyre AN, Arus-Altuz A, Wang S, Singh A, Zhao C, De Naeyer N, DeMarco T, Kuykendall C, Gurley T, Saunders KO, Denny T, Moody MA, Misamore J, Lewis MG, Wiehe K, Cain DW, Montefiori DC, Shaw GM, Williams WB.
Cell Rep. 2023 Mar 14;42(3):112255. doi: 10.1016/j.celrep.2023.112255. Online ahead of print.
PMID:36924501

Stabilized HIV-1 envelope immunization induces neutralizing antibodies to the CD4bs and protects macaques against mucosal infection.

Saunders KO, Edwards RJ, Tilahun K, Manne K, Lu X, Cain DW, Wiehe K, Williams WB, Mansouri K, Hernandez GE, Sutherland L, Scearce R, Parks R, Barr M, DeMarco T, Eater CM, Eaton A, Morton G, Mildenberg B, Wang Y, Rountree RW, Tomai MA, Fox CB, Moody MA, Alam SM, Santra S, Lewis MG, Denny TN, Shaw GM, Montefiori DC, Acharya P, Haynes BF.
Sci Transl Med. 2022 Sep 7;14(661):eabo5598. doi: 10.1126/scitranslmed.abo5598. Epub 2022 Sep 7.
PMID:36070369

Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques.

Walker-Sperling VEK, Mercado NB, Chandrashekar A, Borducchi EN, Liu J, Nkolola JP, Lewis M, Murry JP, Yang Y, Geleziunas R, Robb ML, Michael NL, Pau MG, Wegmann F, Schuitemaker H, Fray EJ, Kumar MR, Siliciano JD, Siliciano RF, Barouch DH.
Nat Commun. 2022 Jun 16;13(1):3463. doi: 10.1038/s41467-022-31196-5.
PMID:35710819

Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques.

Ventura JD, Nkolola JP, Chandrashekar A, Borducchi EN, Liu J, Mercado NB, Hope DL, Giffin VM, McMahan K, Geleziunas R, Murry JP, Yang Y, Lewis MG, Pau MG, Wegmann F, Schuitemaker H, Fray EJ, Kumar MR, Siliciano JD, Siliciano RF, Robb ML, Michael NL, Barouch DH.
NPJ Vaccines. 2022 May 18;7(1):53. doi: 10.1038/s41541-022-00477-x.
PMID:35585080

Two-dose emtricitabine/tenofovir alafenamide plus bictegravir prophylaxis protects macaques against SHIV infection.
Bekerman E, Cox S, Babusis D, Campigotto F, Das M, Barouch DH, Cihlar T, Callebaut C.
J Antimicrob Chemother. 2021 Feb 11;76(3):692-698. doi: 10.1093/jac/dkaa476.
PMID:33202006

A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques.

GALT CD4+PD-1hi T follicular helper (Tfh) cells repopulate after anti-retroviral therapy.
Onabajo OO, Lewis MG, Mattapallil JJ.
Cell Immunol. 2021 Aug;366:104396. doi: 10.1016/j.cellimm.2021.104396. Epub 2021 Jun 16.
PMID: 34157462

GALT CD4+PD-1hi T follicular helper (Tfh) cells repopulate after anti-retroviral therapy.
Onabajo OO, Lewis MG, Mattapallil JJ.
Cell Immunol. 2021 Jun 16;366:104396. doi: 10.1016/j.cellimm.2021.104396. Online ahead of print.
PMID: 34157462

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.
Saunders KO, Pardi N, Parks R, Santra S, Mu Z, Sutherland L, Scearce R, Barr M, Eaton A, Hernandez G, Goodman D, Hogan MJ, Tombacz I, Gordon DN, Rountree RW, Wang Y, Lewis MG, Pierson TC, Barbosa C, Tam Y, Shen X, Ferrari G, Tomaras GD, Montefiori DC, Weissman D, Haynes BF.
NPJ Vaccines. 2021 Apr 9;6(1):50. doi: 10.1038/s41541-021-00307-6.
PMID: 33837212 Free PMC article.

Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques.
Cadena AM, Ventura JD, Abbink P, Borducchi EN, Tuyishime H, Mercado NB, Walker-Sperling V, Siamatu M, Liu PT, Chandrashekar A, Nkolola JP, McMahan K, Kordana N, Hamza V, Bondzie EA, Fray E, Kumar M, Fischinger S, Shin SA, Lewis MG, Siliciano RF, Alter G, Barouch DH.
Nat Commun. 2021 Mar 5;12(1):1474. doi: 10.1038/s41467-021-21724-0.
PMID: 33674572 Free PMC article.

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention and Cure.
Li H, Wang S, Lee FH, Roark RS, Murphy AI, Smith J, Zhao C, Rando J, Chohan N, Ding Y, Kim E, Lindemuth E, Bar KJ, Pandrea I, Apetrei C, Keele BF, Lifson JD, Lewis MG, Denny TN, Haynes BF, Hahn BH, Shaw GM.
J Virol. 2021 Mar 3;95(11):e00071-21. doi: 10.1128/JVI.00071-21. Online ahead of print.
PMID: 33658341 Free PMC article.

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.
Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM.
Science. 2021 Jan 8;371(6525):eabd2638. doi: 10.1126/science.abd2638. Epub 2020 Nov 19.
PMID: 33214287 Free PMC article.

Scientific publication to be published soon – “Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth

Microbial Dysbiosis during SIV Infection is Partially Reverted with Combination Anti-retroviral Therapy

Han Q, Bradley T, Williams WB, Cain DW, Montefiori DC, Saunders KO, Parks RJ, Edwards RW, Ferrari G, Mueller O, Shen X, Wiehe KJ, Reed S, Fox CB, Rountree W, Vandergrift NA, Wang Y, Sutherland LL, Santra S, Moody MA, Permar SR, Tomaras GD, Lewis MG, Van Rompay KKA, Haynes BF. Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization. Cell Rep. 2020
Feb 4;30(5):1553-1569.e6. doi: 10.1016/j.celrep.2019.12.091. PubMedPMID: 32023469.

Saunders KO, Wiehe K, Tian M, Acharya P, Bradley T, Alam SM, Go EP, Scearce R, Sutherland L, Henderson R, Hsu AL, Borgnia MJ, Chen H, Lu X, Wu NR, Watts B, Jiang C, Easterhoff D, Cheng HL, McGovern K, Waddicor P, Chapdelaine-Williams A, Eaton A, Zhang J, Rountree W, Verkoczy L, Tomai M, Lewis MG, Desaire HR, Edwards
RJ, Cain DW, Bonsignori M, Montefiori D, Alt FW, Haynes BF. Targeted selection of HIV-specific antibody mutations by engineering B cell maturation. Science. 2019 Dec 6;366(6470). pii: eaay7199. doi: 10.1126/science.aay7199. PubMed PMID: 31806786.

Abbink P, Mercado NB, Nkolola JP, Peterson RL, Tuyishime H, McMahan K, Moseley ET, Borducchi EN, Chandrashekar A, Bondzie EA, Agarwal A, Belli AJ, Reimann KA, Keele BF, Geleziunas R, Lewis MG, Barouch DH. Lack of therapeutic efficacy of an antibody to α(4)β(7) in SIVmac251-infected rhesus macaques. Science. 2019 Sep 6;365(6457):1029-1033.    

Rosenberg YJ, Lewis GK, Montefiori DC, LaBranche CC, Lewis MG, Urban LA, Lees JP, Mao L, Jiang X. Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques. PLoS One. 2019 Feb 20;14(2):e0212649.

Whitney JB, Lim SY, Osuna CE, Kublin JL, Chen E, Yoon G, Liu PT, Abbink P, Borducci EN, Hill A, Lewis MG, Geleziunas R, Robb ML, Michael NL, Barouch DH. Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy. Nat Commun. 2018 Dec 21;9(1):5429. Borducchi EN, Liu J, Nkolola JP, Cadena AM, Yu WH, Fischinger S, Broge T, Abbink P, Mercado NB, Chandrashekar A, Jetton D, Peter L, McMahan K, Moseley ET, Bekerman E, Hesselgesser J, Li W, Lewis MG, Alter G, Geleziunas R, Barouch DH. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature. 2018 Nov;563(7731):360-364.

Onabajo OO, Lewis MG, Mattapallil JJ. Chronic simian immunodeficiency virus infection is associated with contrasting phenotypes of dysfunctional Bcl6(+) germinal center B cells or Bcl6(-) Bcl2(+) non-germinal center B cells. J Cell Mol Med. 2018 Nov;22(11):5682-5687.

Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E, LaBranche CC, Montefiori DC, Lobby JL, Saunders KO, Liao HX, Korber BT, Sutherland LL, Scearce RM, Hraber PT, Tombácz I, Muramatsu H, Ni H, Balikov DA, Li C, Mui BL, Tam YK, Krammer F, Karikó K, Polacino P, Eisenlohr LC, Madden TD, Hope MJ, Lewis MG, Lee KK, Hu SL, Hensley SE, Cancro MP, Haynes BF, Weissman D. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018 Jun 4;215(6):1571-1588.

Lim SY, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, Barnes TL, Sanisetty S, Seaman MS, Lewis MG, Geleziunas R, Miller MD, Cihlar T, Lee WA, Hill AL, Whitney JB. TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy. Sci Transl Med. 2018 May 2;10(439).

Tuyishime S, Haut LH, Kurupati RK, Billingsley JM, Carnathan D, Gangahara S, Styles TM, Xiang Z, Li Y, Zopfs M, Liu Q, Zhou X, Lewis MG, Amara RR, Bosinger S, Silvestri G, Ertl HCJ. Correlates of Protection Against SIV(mac251) Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors. EBioMedicine. 2018 May;31:25-35

 Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng’ang’a D, Nkolola JP, Brinkman AL, Peter L, Lee BC, Jimenez J, Jetton D, Mondesir J, Mojta S, Chandrashekar A, Molloy K, Alter G, Gerold JM, Hill AL, Lewis MG, Pau MG, Schuitemaker H, Hesselgesser J, Geleziunas R, Kim JH, Robb ML, Michael NL, Barouch DH. Ad26/MVA Therapeutic Vaccination with TLR7 Stimulation in SIV-Infected Rhesus Monkeys. Nature. 2016 Nov 9. doi: 10.1038/nature20583. [Epub ahead of print] PubMed PMID: 27841870.

Liu J, Ghneim K, Sok D, Bosche WJ, Li Y, Chipriano E, Berkemeier B, Oswald K, Borducchi E, Cabral C, Peter L, Brinkman A, Shetty M, Jimenez J, Mondesir J, Lee B, Giglio P, Chandrashekar A, Abbink P, Colantonio A, Gittens C, Baker C, Wagner W, Lewis MG, Li W, Sekaly RP, Lifson JD, Burton DR, Barouch DH. Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus. Science. 2016 Sep 2;353(6303):1045-1049. PubMed PMID: 27540005.

Li H, Wang S, Kong R, Ding W, Lee FH, Parker Z, Kim E, Learn GH, Hahn P, Policicchio B, Brocca-Cofano E, Deleage C, Hao X, Chuang GY, Gorman J, Gardner M, Lewis MG, Hatziioannou T, Santra S, Apetrei C, Pandrea I, Alam SM, Liao HX, Shen X, Tomaras GD, Farzan M, Chertova E, Keele BF, Estes JD, Lifson JD, Doms RW, Montefiori DC, Haynes BF, Sodroski JG, Kwong PD, Hahn BH, Shaw GM. Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3413-22. doi: 10.1073/pnas.1606636113. PubMed PMID: 27247400.

Barouch DH, Ghneim K, Bosche WJ, Li Y, Berkemeier B, Hull M, Bhattacharyya S, Cameron M, Liu J, Smith K, Borducchi E, Cabral C, Peter L, Brinkman A, Shetty M, Li H, Gittens C, Baker C, Wagner W, Lewis MG, Colantonio A, Kang HJ, Li W, Lifson JD, Piatak M Jr, Sekaly RP. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys. Cell. 2016 Apr 21;165(3):656-67. doi: 10.1016/j.cell.2016.03.021. PubMed PMID: 27085913.

Barouch DH, Alter G, Broge T, Linde C, Ackerman ME, Brown EP, Borducchi EN, Smith KM, Nkolola JP, Liu J, Shields J, Parenteau L, Whitney JB, Abbink P, Ng’ang’a DM, Seaman MS, Lavine CL, Perry JR, Li W, Colantonio AD, Lewis MG, Chen B, Wenschuh H, Reimer U, Piatak M, Lifson JD, Handley SA, Virgin HW, Koutsoukos M, Lorin C, Voss G, Weijtens M, Pau MG, Schuitemaker H. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science. 2015 Jul 17;349(6245):320-4. doi: 10.1126/science.aab3886. PubMed PMID: 26138104.

Shytaj IL, Nickel G, Arts E, Farrell N, Biffoni M, Pal R, Chung HK, LaBranche C, Montefiori D, Vargas-Inchaustegui D, Robert-Guroff M, Lewis MG, Sacha JB, Palamara AT, Savarino A. Two-Year Follow-Up of Macaques Developing Intermittent Control of the Human Immunodeficiency Virus Homolog Simian Immunodeficiency Virus SIVmac251 in the Chronic Phase of Infection. J Virol. 2015 Aug;89(15):7521-35.doi: 10.1128/JVI.00396-15. PubMed PMID: 25972547.

Asmal M, Luedemann C, Lavine CL, Mach LV, Balachandran H, Brinkley C, Denny TN, Lewis MG, Andersen H, Pal R, Sok D, Le K, Pauthner M, Hahn BH, Shaw GM, Seaman MS, Letvin NL, Burton DR, Sodroski JG, Haynes BF, Santra S. Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes. Virology. 2015 Jan 15;475:37-45. doi: 10.1016/j.virol.2014.10.032. PubMed PMID: 25462344.

Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, Parenteau L, Cabral C, Shields J, Blackmore S, Smith JY, Brinkman AL, Peter LE, Mathew SI, Smith KM, Borducchi EN, Rosenbloom DI, Lewis MG, Hattersley J, Li B, Hesselgesser J, Geleziunas R, Robb ML, Kim JH, Michael NL, Barouch DH. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014 Aug 7;512(7512):74-7. doi: 10.1038/nature13594. PubMed PMID: 25042999.

Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, Liu J, Stephenson KE, Chang HW, Shekhar K, Gupta S, Nkolola JP, Seaman MS, Smith KM, Borducchi EN, Cabral C, Smith JY, Blackmore S, Sanisetty S, Perry JR, Beck M, Lewis MG, Rinaldi W, Chakraborty AK, Poignard P, Nussenzweig MC, Burton DR. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013 Nov 14;503(7475):224-8. doi: 0.1038/nature12744. PubMed PMID: 24172905.