Contact PI: Kristina De Paris PhD, UNC Chapel Hill

Leveraging the infant immune system for the induction of broadly neutralizing antibodies

The goal is to identify early determinants that are critical for the induction of HIV bNAbs by vaccination.

Role: MPI

*Publications are not available at this time.

Early life vaccination to prevent HIV acquisition during adolescence

MPI: Kristina De Paris, UNC Chapel Hill

Role: Contact PI, Project Lead

1. Jiang D, Goswami R, Dennis M, Heimsath H, Kozlowski PA, Ardeshir A, Van Rompay KKA, De Paris K, Permar SR, Surana NK. Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques. Front Immunol. 2023 Dec 6;14:1283343. doi: 10.3389/fimmu.2023.1283343. PMID: 38124733; PMCID: PMC10731017.

2. Milligan EC, Olstad K, Williams CA, Mallory M, Cano P, Cross KA, Munt JE, Garrido C, Lindesmith L, Watanabe J, Usachenko JL, Hopkins L, Immareddy R, Shaan Lakshmanappa Y, Elizaldi SR, Roh JW, Sammak RL, Pollard RE, Yee JL, Herbek S, Scobey T, Miehlke D, Fouda G, Ferrari G, Gao H, Shen X, Kozlowski PA, Montefiori D, Hudgens MG, Edwards DK, Carfi A, Corbett KS, Graham BS, Fox CB, Tomai M, Iyer SS, Baric R, Reader R, Dittmer DP, Van Rompay KKA, Permar SR, De Paris K. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med. 2023 Mar;15(685):eadd6383. doi: 10.1126/scitranslmed.add6383. Epub 2023 Mar 1. PMID: 36454813; PMCID: PMC9765459.

3. De Paris K, Permar SR. Routine SARS-CoV-2 vaccination for all children. Immunol Rev. 2022 Aug;309(1):90-96. doi: 10.1111/imr.13108. Epub 2022 Jul 7. PMID: 35799475; PMCID: PMC9339529.

4. Nelson AN, Dennis M, Mangold JF, Li K, Saha PT, Cronin K, Cross KA, Kumar A, Mangan RJ, Shaw GM, Bar KJ, Haynes B, Moody AM, Munir Alam S, Pollara J, Hudgens MG, Van Rompay KKA, De Paris K, Permar SR. Leveraging antigenic seniority for maternal vaccination to prevent mother-to-child transmission of HIV-1. NPJ Vaccines. 2022 Jul 30;7(1):87. doi: 10.1038/s41541-022-00505-w. PMID: 35907918; PMCID: PMC9338948.

5. Vijayan KKV, Cross KA, Curtis AD 2nd, Van Rompay KKA, Pollara J, Fox CB, Tomai M, Hanke T, Fouda G, Hudgens MG, Permar SR, De Paris K. Early Post- Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope-Specific Plasma Antibodies in Infant Rhesus Macaques. Front Immunol. 2022 Apr 27;13:840976. doi: 10.3389/fimmu.2022.840976. PMID: 35572573; PMCID: PMC9094446.

6. Curtis AD 2nd, Saha PT, Dennis M, Berendam SJ, Ramasubramanian P, Cross KA, Alam SM, Ferrari G, Kozlowski PA, Fouda GG, Hudgens MG, Van Rompay KKA, Pollara J, Permar SR, De Paris K. Vaccine-Induced, High-Magnitude HIV Env-Specific Antibodies with Fc-Mediated Effector Functions Are Insufficient to Protect Infant Rhesus Macaques against Oral SHIV Infection. mSphere. 2022 Feb 23;7(1):e0083921. doi: 10.1128/msphere.00839-21. Epub 2022 Feb 23. PMID: 35196125; PMCID: PMC8865927.

7. Berendam SJ, Morgan-Asiedu PK, Mangan RJ, Li SH, Heimsath H, Luo K, Curtis AD 2nd, Eudailey JA, Fox CB, Tomai MA, Phillips B, Itell HL, Kunz E, Hudgens M, Cronin K, Wiehe K, Alam SM, Van Rompay KKA, De Paris K, Permar SR, Moody MA, Fouda GG. Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques. PLoS One. 2021 Dec 31;16(12):e0256885. doi: 10.1371/journal.pone.0256885. PMID: 34972105; PMCID: PMC8719683.

8. Garrido C, Curtis AD 2nd, Dennis M, Pathak SH, Gao H, Montefiori D, Tomai M, Fox CB, Kozlowski PA, Scobey T, Munt JE, Mallory ML, Saha PT, Hudgens MG, Lindesmith LC, Baric RS, Abiona OM, Graham B, Corbett KS, Edwards D, Carfi A, Fouda G, Van Rompay KKA, De Paris K, Permar SR. SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques. Sci Immunol. 2021 Jun 15;6(60):eabj3684. doi: 10.1126/sciimmunol.abj3684. PMID: 34131024; PMCID: PMC8774290.

9. Curtis AD 2nd, Dennis M, Eudailey J, Walter KL, Cronin K, Alam SM, Choudhary N, Tuck RH, Hudgens M, Kozlowski PA, Pollara J, Ferrari G, Van Rompay KKA, Permar S, De Paris K. HIV Env-Specific IgG Antibodies Induced by Vaccination of Neonatal Rhesus Macaques Persist and Can Be Augmented by a Late Booster Immunization in Infancy. mSphere. 2020 Mar 25;5(2):e00162-20. doi: 10.1128/mSphere.00162-20. PMID: 32213623; PMCID: PMC7096624.

10. Fouda GG, De Paris K, Levy O, Marchant A, Gray G, Permar S, Marovich M, Singh A. Immunological mechanisms of inducing HIV immunity in infants. Vaccine. 2020 Jan 16;38(3):411-415. doi: 10.1016/j.vaccine.2019.11.011. Epub 2019 Nov 21. PMID: 31761501; PMCID: PMC6955149.

11. Jones DI, Pollara JJ, Johnson-Weaver BT, LaBranche CC, Montefiori DC, Pickup DJ, Permar SR, Abraham SN, Maddaloni M, Pascual DW, Staats HF. Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen. J Virol. 2019 Jun 28;93(14):e00475-19. doi: 10.1128/JVI.00475-19. PMID: 31068425; PMCID: PMC6600201.

12. Martinez DR, Fong Y, Li SH, Yang F, Jennewein MF, Weiner JA, Harrell EA, Mangold JF, Goswami R, Seage GR 3rd, Alter G, Ackerman ME, Peng X, Fouda GG, Permar SR. Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women. Cell. 2019 Jun 27;178(1):190-201.e11. doi: 10.1016/j.cell.2019.05.046. Epub 2019 Jun 13. PMID: 31204101; PMCID: PMC6727200.

13. Dennis M, Eudailey J, Pollara J, McMillan AS, Cronin KD, Saha PT, Curtis AD, Hudgens MG, Fouda GG, Ferrari G, Alam M, Van Rompay KKA, De Paris K, Permar S, Shen X. Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques. J Virol. 2019 Feb 19;93(5):e01783-18. doi: 10.1128/JVI.01783-18. PMID: 30541851; PMCID: PMC6384077.

14. Nelson CS, Fouda GGA, Permar SR. Pediatric HIV-1 Acquisition and Lifelong Consequences of Infant Infection. Curr Immunol Rev. 2019;15(1):131-138. doi: 10.2174/1573395514666180531074047. PMID: 33223981; PMCID: PMC7678020.

15. Himes JE, Goswami R, Mangan RJ, Kumar A, Jeffries TL Jr, Eudailey JA, Heimsath H, Nguyen QN, Pollara J, LaBranche C, Chen M, Vandergrift NA, Peacock JW, Schiro F, Midkiff C, Ferrari G, Montefiori DC, Hernandez XA, Aye PP, Permar SR. Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys. Mucosal Immunol. 2018 Nov;11(6):1716-1726. doi: 10.1038/s41385-018-0067-7. Epub 2018 Aug 16. PMID: 30115994; PMCID: PMC6420805.

16. Phillips B, Van Rompay KKA, Rodriguez-Nieves J, Lorin C, Koutsoukos M, Tomai M, Fox CB, Eudailey J, Dennis M, Alam SM, Hudgens M, Fouda G, Pollara J, Moody A, Shen X, Ferrari G, Permar S, De Paris K. Adjuvant-Dependent Enhancement of HIV Env-Specific Antibody Responses in Infant Rhesus Macaques. J Virol. 2018 Sep 26;92(20):e01051-18. doi: 10.1128/JVI.01051-18. PMID: 30089691; PMCID: PMC6158427.

17. Permar S, Levy O, Kollman TR, Singh A, De Paris K. Early Life HIV-1 Immunization: Providing a Window for Protection Before Sexual Debut. AIDS Res Hum Retroviruses. 2018 Oct;34(10):823-827. doi: 10.1089/AID.2018.0018. Epub 2018 Jul 3. PMID: 29860868; PMCID: PMC6204561.

18. Eudailey JA, Dennis ML, Parker ME, Phillips BL, Huffman TN, Bay CP, Hudgens MG, Wiseman RW, Pollara JJ, Fouda GG, Ferrari G, Pickup DJ, Kozlowski PA, Van Rompay KKA, De Paris K, Permar SR. Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques. mSphere. 2018 Jan 10;3(1):e00505-17. doi: 10.1128/mSphere.00505-17. PMID: 29359183; PMCID: PMC5760748.

19. Phillips B, Fouda GG, Eudailey J, Pollara J, Curtis AD 2nd, Kunz E, Dennis M, Shen X, Bay C, Hudgens M, Pickup D, Alam SM, Ardeshir A, Kozlowski PA, Van Rompay KKA, Ferrari G, Moody MA, Permar S, De Paris K. Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine- Elicited Antibody Magnitude and Function in Infant Macaques. Clin Vaccine Immunol. 2017 Oct 5;24(10):e00231-17. doi: 10.1128/CVI.00231-17. PMID: 28814388; PMCID: PMC5629672.

20. Nguyen QN, Himes JE, Martinez DR, Permar SR. The Impact of the Gut Microbiota on Humoral Immunity to Pathogens and Vaccination in Early Infancy. PLoS Pathog. 2016 Dec 22;12(12):e1005997. doi: 10.1371/journal.ppat.1005997. PMID: 28006021; PMCID: PMC5179050.

21. Zhang R, Martinez DR, Nguyen QN, Pollara J, Arifin T, Stolarchuk C, Foulger A, Amos JD, Parks R, Himes JE, Wang M, Edwards RW, Trama AM, Vandergrift N, Colvin L, Dewar K, Juretic N, Wasserscheid J, Ferrari G, Liao HX, Permar SR. Envelope-specific B-cell populations in African green monkeys chronically infected with simian immunodeficiency virus. Nat Commun. 2016 Jul 6;7:12131. doi: 10.1038/ncomms12131. PMID: 27381634; PMCID: PMC4935802.

22. Nelson CS, Pollara J, Kunz EL, Jeffries TL Jr, Duffy R, Beck C, Stamper L, Wang M, Shen X, Pickup DJ, Staats HF, Hudgens MG, Kepler TB, Montefiori DC, Moody MA, Tomaras GD, Liao HX, Haynes BF, Ferrari G, Fouda GGA, Permar SR. Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk. J Virol. 2016 Apr 29;90(10):4951-4965. doi: 10.1128/JVI.00335-16. PMID: 26937027; PMCID: PMC4859715.

23. Fouda GG, Cunningham CK, Permar SR. Infant HIV-1 vaccines: supplementing strategies to reduce maternal-child transmission. JAMA. 2015 Apr 21;313(15):1513-4. doi: 10.1001/jama.2015.1382. PMID: 25898044; PMCID: PMC4520313.

Immunologic and virologic determinants of congenital Cytomegalovirus transmission and disease in rhesus monkeys

Role: PI, Core 1 and Project 1 Lead

1. Otero CE, Barfield R, Scheef E, Nelson CS, Rodgers N, Wang HY, Moström MJ, Manuel TD, Sass J, Schmidt K, Taher H, Papen C, Sprehe L, Kendall S, Davalos A, Barry PA, Früh K, Pollara J, Malouli D, Chan C, Kaur A, Permar SR. Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. PLoS Pathog. 2023 Oct 23;19(10):e1011378. doi: 10.1371/journal.ppat.1011378. PMID: 37871009; PMCID: PMC10621917.

2. Moström MJ, Yu S, Tran D, Saccoccio FM, Versoza CJ, Malouli D, Mirza A, Valencia S, Gilbert M, Blair RV, Hansen S, Barry P, Früh K, Jensen JD, Pfeifer SP, Kowalik TF, Permar SR, Kaur A. Protective effect of pre-existing natural immunity in a nonhuman primate reinfection model of congenital cytomegalovirus infection. PLoS Pathog. 2023 Oct 5;19(10):e1011646. doi: 10.1371/journal.ppat.1011646. PMID: 37796819; PMCID: PMC10553354.

3. Gong Y, Moström M, Otero C, Valencia S, Tarantal AF, Kaur A, Permar SR, Chan C. Mathematical Modeling of Rhesus Cytomegalovirus Transplacental Transmission in Seronegative Rhesus Macaques. Viruses. 2023 Oct 1;15(10):2040. doi: 10.3390/v15102040. PMID: 37896817; PMCID: PMC10611067.

4. Rosenberg YJ, Ordonez T, Khanwalkar US, Barnette P, Pandey S, Backes IM, Otero CE, Goldberg BS, Crowley AR, Leib DA, Shapiro MB, Jiang X, Urban LA, Lees J, Hessell AJ, Permar S, Haigwood NL, Ackerman ME. Evidence for the Role of a Second Fc-Binding Receptor in Placental IgG Transfer in Nonhuman Primates. mBio. 2023 Apr 25;14(2):e0034123. doi: 10.1128/mbio.00341-23. Epub 2023 Mar 22. PMID: 36946726; PMCID: PMC10127586.

5. Hansen SG, Womack JL, Perez W, Schmidt KA, Marshall E, Iyer RF, Cleveland Rubeor H, Otero CE, Taher H, Vande Burgt NH, Barfield R, Randall KT, Morrow D, Hughes CM, Selseth AN, Gilbride RM, Ford JC, Caposio P, Tarantal AF, Chan C, Malouli D, Barry PA, Permar SR, Picker LJ, Früh K. Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV. JCI Insight. 2023 Mar 22;8(6):e164692. doi: 10.1172/jci.insight.164692. PMID: 36749635; PMCID: PMC10070102.

6. Harnois MJ, Dennis M, Stöhr D, Valencia SM, Rodgers N, Semmes EC, Webster HS, Jenks JA, Barfield R, Pollara J, Chan C, Sinzger C, Permar SR. Characterization of Plasma Immunoglobulin G Responses in Elite Neutralizers of Human Cytomegalovirus. J Infect Dis. 2022 Nov 1;226(9):1667-1677. doi: 10.1093/infdis/jiac341. PMID: 35970817; PMCID: PMC10205896.

7. Hu X, Wang HY, Otero CE, Jenks JA, Permar SR. Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development. Annu Rev Virol. 2022 Sep 29;9(1):491-520. doi: 10.1146/annurev-virology-100220-010653. Epub 2022 Jun 15. PMID: 35704747.

8. Permar SR, Kaur A, Fruh K. Derisking. Human Cytomegalovirus Vaccine Clinical Development in Relevant Preclinical Models. J Infect Dis. 2022 Sep 4;226(4):563-565. doi: 10.1093/infdis/jiac131. PMID: 35415750; PMCID: PMC9441196.

9. Li M, Brokaw A, Furuta AM, Coler B, Obregon-Perko V, Chahroudi A, Wang HY, Permar SR, Hotchkiss CE, Golos TG, Rajagopal L, Adams Waldorf KM. Non-human Primate Models to Investigate Mechanisms of Infection-Associated Fetal and Pediatric Injury, Teratogenesis and Stillbirth. Front Genet. 2021 Jul 5;12:680342. doi: 10.3389/fgene.2021.680342. PMID: 34290739; PMCID: PMC8287178.

10. Wang HY, Valencia SM, Pfeifer SP, Jensen JD, Kowalik TF, Permar SR. Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity. Viruses. 2021 Jun 9;13(6):1106. doi: 10.3390/v13061106. PMID: 34207868; PMCID: PMC8227702.

11. Singh T, Otero CE, Li K, Valencia SM, Nelson AN, Permar SR. Vaccines for Perinatal and Congenital Infections-How Close Are We? Front Pediatr. 2020 Dec 15;8:569. doi: 10.3389/fped.2020.00569. PMID: 33384972; PMCID: PMC7769834.

12. Jenks JA, Nelson CS, Roark HK, Goodwin ML, Pass RF, Bernstein DI, Walter EB, Edwards KM, Wang D, Fu TM, An Z, Chan C, Permar SR. Antibody binding to native cytomegalovirus glycoprotein B predicts efficacy of the gB/MF59 vaccine in humans. Sci Transl Med. 2020 Nov 4;12(568):eabb3611. doi: 10.1126/scitranslmed.abb3611. PMID: 33148624; PMCID: PMC8058742.

13. Vera Cruz D, Nelson CS, Tran D, Barry PA, Kaur A, Koelle K, Permar SR. Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission. PLoS Pathog. 2020 Feb 14;16(2):e1007968. doi: 10.1371/journal.ppat.1007968. PMID: 32059027; PMCID: PMC7046290.

14. Jenks JA, Goodwin ML, Permar SR. The Roles of Host and Viral Antibody Fc Receptors in Herpes Simplex Virus (HSV) and Human Cytomegalovirus (HCMV) Infections and Immunity. Front Immunol. 2019 Sep 6;10:2110. doi: 10.3389/fimmu.2019.02110. PMID: 31555298; PMCID: PMC6742691.

PI: Worgall, Stefan

Impact of SARS-CoV-2 infection on respiratory viral immune responses in children with and without asthma

This application will study how highly SARS-CoV-2 exposed NYC children of all ages and with asthma react to common cold viruses to understand the implications of natural infection on subsequent respiratory virus infections, as well as reinfections with SARS-CoV-2 variants.

Role: MPI

*Publications are not available at this time.

MPI: Matthew Kelly MD MPH, Duke University

Contact PI: Genevieve Fouda Md PhD

Early life B cell responses and inflammation following SARS-CoV-2 infection

Role: MPI

*Publications are not available at this time

Escape of maternal plasma broadly neutralizing antibody as a mechanism of mother to child HIV transmission

Role: PI

1. Tu JJ, Kumar A, Giorgi EE, Eudailey J, LaBranche CC, Martinez DR, Fouda GG, Moreau Y, Thomas A, Montefiori D, Gao F, Sagar M, Permar SR. Vertical HIV-1 Transmission in the Setting of Maternal Broad and Potent Antibody Responses. J Virol. 2022 Jun 8;96(11):e0023122. doi: 10.1128/jvi.00231-22. Epub 2022 May 10. PMID: 35536018; PMCID: PMC9175633.

2. Kumar A, Giorgi EE, Tu JJ, Martinez DR, Eudailey J, Mengual M, Honnayakanahalli Marichannegowda M, Van Dyke R, Gao F, Permar SR. Mutations that confer resistance to broadly-neutralizing antibodies define HIV-1 variants of transmitting mothers from that of non-transmitting mothers. PLoS Pathog. 2021 Apr 2;17(4):e1009478. doi: 10.1371/journal.ppat.1009478. PMID: 33798244; PMCID: PMC8055002.

Identifying and modeling immune correlates of protection against congenital CMV transmission after primary maternal infection

Role: PI

*Publications are not available at this time

MPIs:

R. Keith Reeves, Duke

Amitinder (Miti) Kaur, Tulane

Role of maternal-fetal interface NK cells in pregnancy maintenance and congenital CMV transmission

Role: MPI

1. Moström MJ, Yu S, Tran D, Saccoccio FM, Versoza CJ, Malouli D, Mirza A, Valencia S, Gilbert M, Blair RV, Hansen S, Barry P, Früh K, Jensen JD, Pfeifer SP, Kowalik TF, Permar SR, Kaur A. Protective effect of pre-existing natural immunity in a nonhuman primate reinfection model of congenital cytomegalovirus infection. PLoS Pathog. 2023 Oct 5;19(10):e1011646. doi: 10.1371/journal.ppat.1011646. PMID: 37796819; PMCID: PMC10553354.

Improving HCMV vaccine-elicited immunity by targeting viral Fc receptors

Role: PI

*Publications are not available at this time.

Tri-I Stimulating Access to Research in Residency program (Tri-I StARR - NIAID)

Role: MPI

*Publications are not available at this time.