CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

428

ChAdOx1.HIVconsvX and MVA.HIVconsvX Vaccination Is Safe and Immunogenic in PWH on ART: The CM Study Cynthia L. Gay 1 , Yinyan Xu 1 , Ann Marie Weideman 1 , Shayla Conrad 1 , Fiona Shaw 1 , Sofia Mariano 1 , Melissa Mischell 1 , Susan Pedersen 1 , Alexander Bradley 1 , Ally Odom 2 , Michael Hudgens 1 , Mehri McKellar 3 , Emmanual Walter 2 , Tomáš Hanke 4 , Nilu Goonetilleke 1 1 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 2 Duke Human Vaccine Institute, Durham, NC, USA, 3 Duke University Medical Center, Durham, NC, USA, 4 University of Oxford, Oxford, UK Background: Durable antiviral therapy (ART)-free remission from HIV-1 will likely require a robust and targeted T-cell response to limit viral reactivation. Serial vaccination with different viral vectors expressing the same immunogen has induced higher T-cell frequencies than homologous vaccination regimens. Methods: The CM study is a double-blind, randomized, phase I vaccine trial which recruited people with HIV (PWH) suppressed on ART for >24 months. The study vaccines were ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) at 28 days, all given intramuscularly. Vaccines expressed conserved Gag and Pol regions as mosaic 1 (C1 and M3) and mosaic 2 (C62 and M4), which differed in ~8% of amino acids. Participants were randomized to regimens C62-M4 (mosaic 1), C1C62-M3M4 (mosaics 1 and 2) or placebo (Table 1). Exclusion criteria included history of clotting disorders and prior vaccination with MVA-mpox and ChAdOx1 nCoV-19 vaccines. Immunogenicity endpoints were measured using IFN-γ ELISpot. Results: Enrollment is complete with 18 participants 24-67 years of age, 16.7% female, 44% black/AA; but the blind is maintained. Thirteen of 18 participants completed all study visits. Remaining participants have completed vaccination visits and at least 28 days of safety follow-up after M3 or M3M4 boost vaccination. The final study visit is scheduled for Jan 2025. Adverse events (AEs) following vaccination were mostly Grade I and resolved within 48 hours. One AE of special interest possibly related to the products was observed. No serious AEs occurred. ELISpot assays have been completed for 12 participants. Ten of the 12 participants exhibited strong increases in T-cell responses (>2 to 16-fold) to mosaic-1/2 immunogens at two weeks post M4 or M3M4 boosting. In most participants, HIV-1-specific T-cell breadth and the proportion of the total HIV specific T-cell response targeting the HIVconsvX conserved regions increased after M4 or M3M4 vaccination. HIV-1-specific T-cell proliferation (CSFE) also consistently increased following vaccination. Conclusions: We present the first results following vaccination with C62-M4 and C1C62-M3M4 in PWH on ART. Vaccination was safe and immunogenic. Analysis of unblinded safety and immunogenicity data for all study participants will be presented.

can mimic APC to activate and selectively expand HIV (SL9), CMV (NLV) or CoV-2 (YLQ)-specific CD8 T cells. Expansion of virus-specific CD8 T cells was determined by tetramer staining. Cytotoxicity against peptide-loaded T2 cells and cytokine production were determined by flow cytometry. Viral suppression assays were performed using HIV and CMV with luciferase gene reporters. Results: In vitro treatment of PBMC (n=2-5 donors) with VirTac presenting HIV-, CMV- or CoV-2-peptide MHC constructs markedly expanded the fraction of CD8 T cells that were HIV-specific (up to 23%) CMV-specific (up to 87%) or CoV2 specific (up to 67%), respectively (Fig. 1A, upper panel). Intravenous infusion of HIV- or CMV-VirTacs expanded HIV- and CMV-specific T cells, respectively, by ~30-fold in NSG mice intrasplenically engrafted with donor PBMCs (Fig. 1A, lower panel). Inclusion of agonist αCD28 scFv in the HIV-, CMV- or CoV-2-VirTacs increased in vitro or in vivo expansion of HIV-, CMV- or CoV-2-specific CD8 T cells in some donors. Antigen-specific T cells expanded with VirTac were highly functional, displaying potent cytotoxic capacity (Fig. 1B), antigen-specific IFNg and TNFα production and suppression of in vitro HIV or CMV infections. Conclusions: VirTac represents a flexible and robust platform for the ex vivo expansion of CD8 T cells targeting HIV and other viral-derived epitopes for adoptive cell transfer. This strategy may also support in vivo modulation to provide sustained anti-HIV activity and enable personalized antigen-specific strategies to achieve a functional cure for HIV. Therapeutic HIV Vaccine ± TLR4 Adjuvant Impact on Monocyte Subsets in Early-Treated Youths With HIV Alessia Neri 1 , Giulio Olivieri 2 , Chiara Pighi 2 , Arianna Rotili 1 , Sarah Moreland 3 , Elena Morrocchi 1 , Suteeraporn Pinyakorn 4 , Glenna Schluck 4 , Ellen Turk 3 , Shaun Barnabas 5 , Mark Cotton 5 , Mark de Souza 6 , Nicola Cotugno 2 , Merlin Robb 4 , Paolo Palma 2 1 University of Rome Tor Vergata, Rome, Italy, 2 Ospedale Pediatrico Bambino Gesu, Rome, Italy, 3 Walter Reed Army Institute of Research, Silver Spring, MD, USA, 4 US Military HIV Research Program, Bethesda, MD, USA, 5 Family Clinical Research Unit, Tygerberg, South Africa, 6 Institute of HIV Research and Innovation, Bangkok, Thailand Background: Monocytes (MO) play a crucial role in restricting HIV replication and spread. After HIV acquisition, MO show increased activation and differentiation, altering subset distribution despite ART. MO enhance vaccine induced immune responses and contribute to trained immunity, boosting protection. We here investigated changes in MO phenotype in a therapeutic vaccine study. Methods: HVRRICANE is the 1st pediatric combined (HIVIS DNA + MVA CMDR) therapeutic HIV vaccine ± Cervarix co-administration to provide TLR4 immunoadjuvant. 25 adolescents with perinatal HIV, suppressed on ART (since 6 months of age) were enrolled (Fig.1). Comprehensive phenotypic analysis of the MO populations was conducted across the entire cohort using a new gating strategy based on CD86, CCR2, HLA-DR, CD64, and CD33 expression. Data acquisition was performed using a BD Symphony A3 cell analyzer through multi parametric approach. High dimensional analyses concatenating all participant events at baseline and weeks 16, 36, and 48 identified 8 cells clusters, analyzed via t-SNE for marker expression and temporal trends (Fig.1). Results: Classical (CL, CD86+CD64 high CCR2+HLADR low ) MO showed a significant longitudinal increase (p=0.034) only in Arm 1 (no TLR4 agonist) from a baseline median of 38.4%, peaking at wk 8 (51.6%), and remained elevated at wk 48 (44.3%). This increase was accompanied by a waning trend in the Intermediate (ITM; CD86+CD64 high CCR2 low HLADR high ), from a baseline of 2.57% and reaching 1.09% at wk 48. Arm 1 also showed significant (p=0.034) changes in CD93 geometric mean fluorescence intensity (gMFI) on CL MO over time. This subset presented lower CD49d gMFI at weeks 16 (p=0.045), 40 (p=0.031) and 48 (p=0.038) in Arm 1 than to Arm 2 (with TLR4 agonist), while CD11a gMFI was higher (p=0.037) in Arm 1 at wk 40. In contrast, Arm 3 (only TLR4 agonist) showed an increasing trend in non-classical (NC; CD86+CD64 low CD33 low ) MO, confirmed by higher (p=0.043) Ki67 gMFI at wk 36 than to Arm 1. Additionally, in the ITM subset, Arm 2 exhibited a substantial (p= 0.028) increase in CD11b gMFI, peaking at wk 48; while Arm 1 demonstrated a significant (p=0.009) decrease in CD11c gMFI above the on ITM MO over time. Conclusions: We observed distinct MO subset distribution and integrin/ receptor expression following DNA prime and MVA boost vaccination regimens with Cervarix® co-administration. The figure, table, or graphic for this abstract has been removed.

Poster Abstracts

430

429

A Novel Immunotherapeutic Platform for Amplifying HIV, CMV, or SARS-CoV-2-Specific T-Cell Responses Marta Santos Bravo, Erin Cole, April Mueller, Christopher Hiner, Agnes Sydenstricker, Adilyn Voss, Jian Hua, Scott Gartforth, Steven Almo, Harris Goldstein Albert Einstein College of Medicine, Bronx, NY, USA Background: While adoptive cell transfer of HIV-specific T cells is a promising immunotherapy to provide a functional cure for HIV, its development and broader application is limited by the cost, logistical complexity, and variability of current methods for ex vivo expansion of HIV-specific T cells. To address these needs, we describe a novel modular and highly scalable lentiviral-based immunotherapeutic platform, VirTac (Viral particle-based T cell Activator), which consist of lentiviral particles (LVP) containing integral membrane proteins for the ex vivo and in vivo expansion of viral-specific T cells recognizing highly conserved virus-derived peptide antigens. Methods: We constructed plasmids encoding single chain HLA-A*0201 MHC molecules tethered to viral-derived peptides, either alone (modless) or in combination with an agonist αCD28 scFv, to generate non-infectious LVP that

CROI 2025 103