Dominic Paquin-Proulx, PhD
Our laboratory focuses on understanding how the innate cells respond to viral vectors and adjuvants used in HIV vaccine using advanced flow cytometry with the goal of leveraging their modulatory functions to boost the immune response. Invariant Natural Killer T (iNKT) and Mucosal Associated Invariant T (MAIT) cells are innate T cells that recognize structures conserved across pathogens and are restricted by CD1d and MR1 respectively. These cells represent an important first line of defense against pathogens and have the capacity to modulate the adaptive immune response. Natural killer (NK) cells are considered vital to early protection from diseases and support development of adaptive immune responses. However, less is known regarding NK cells response to vaccine.
We aim to understand how adaptive and antigen specific NK cells may arise following different vaccine regimen and their potential role in preventing infection. The Fc domain of antibodies can modulate cellular effector functions through interactions with Fc receptors (FcR) on innate immune cells. These interactions can result in activation of Ab-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), complement deposition (ADCD), and pro-inflammatory cytokine production. Following the results of RV144, there is a growing understanding that these antibody effector functions are contributing to prevention of HIV infection.
Our laboratory has developed high throughput assays to measure these functions from clinical trial samples. We are also investigating how adjuvant and innate immune cell sensing can be leveraged to further enhance these functions.
Postdoc: Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
Mosaic vaccine-induced antibody-dependent cellular phagocytosis associated with delayed HIV-1 viral load rebound post treatment interruption. Mdluli T, Slike BM, Curtis DJ, Shubin Z, Tran U, Li Y, Dussupt V, Mendez-Rivera L, Pinyakorn S, Stieh DJ, Tomaka FL, Schuitemaker H, Pau MG, Colby DJ, Kroon E, Sacdalan C, de Souza M, Phanupak N, Hsu DC, Ananworanich J, Ake JA, Trautmann L, Vasan S, Robb ML, Krebs SJ, Paquin-Proulx D, Rolland M. Cell Rep. 2024 Jun 25;43(6):114344. doi: 10.1016/j.celrep.2024.114344. Epub 2024 Jun 8. PMID: 38850529 |
Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production. N'guessan KF, Machmach K, Swafford I, Costanzo MC, Wieczorek L, Kim D, Akapirat S, Polonis VR, Pitisuttithum P, Nitayaphan S, Gurunathan S, Sinangil F, Chariyalertsak S, Ake JA, O'connell RJ, Vasan S, Paquin-Proulx D. Front Immunol. 2024 Feb 13;15:1339727. doi: 10.3389/fimmu.2024.1339727. eCollection 2024. PMID: 38420129 |
Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability. Shubin Z, Stanfield-Oakley S, Puangkaew J, Pitisutthithum P, Nitayaphan S, Gurunathan S, Sinangil F, Chariyalertsak S, Phanuphak N, Ake JA, O'Connell RJ, Vasan S, Akapirat S, Eller MA, Ferrari G, Paquin-Proulx D; RV306 Study Group. AIDS. 2023 Aug 1;37(10):1519-1524. doi: 10.1097/QAD.0000000000003611. Epub 2023 Jun 1. PMID: 37260254 |
Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa. Paquin-Proulx D, Lal KG, Phuang-Ngern Y, Creegan M, Tokarev A, Suhkumvittaya S, Alrubayyi A, Kroon E, Pinyakorn S, Slike BM, Bolton DL, Krebs SJ, Eller LA, Sajjaweerawan C, Pagliuzza A, Chomont N, Rerknimitr R, Chomchey N, Phanuphak N, de Souza MS, Michael NL, Robb ML, Ananworanich J, Sandberg JK, Eller MA, Schuetz A; RV217; RV254/SEARCH010; RV304/SEARCH013; Study Groups. Proc Natl Acad Sci U S A. 2021 Nov 16;118(46):e2104721118. doi: 10.1073/pnas.2104721118. PMID: 34753817 |
Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations. Dussupt V, Sankhala RS, Mendez-Rivera L, Townsley SM, Schmidt F, Wieczorek L, Lal KG, Donofrio GC, Tran U, Jackson ND, Zaky WI, Zemil M, Tritsch SR, Chen WH, Martinez EJ, Ahmed A, Choe M, Chang WC, Hajduczki A, Jian N, Peterson CE, Rees PA, Rutkowska M, Slike BM, Selverian CN, Swafford I, Teng IT, Thomas PV, Zhou T, Smith CJ, Currier JR, Kwong PD, Rolland M, Davidson E, Doranz BJ, Mores CN, Hatziioannou T, Reiley WW, Bieniasz PD, Paquin-Proulx D, Gromowski GD, Polonis VR, Michael NL, Modjarrad K, Joyce MG, Krebs SJ. Nat Immunol. 2021 Dec;22(12):1503-1514. doi: 10.1038/s41590-021-01068-z. Epub 2021 Oct 29. PMID: 34716452 |