CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

differences were not observable between the 3 groups (p=0.53). 13 peptides failed to induce GB in any individual. Conclusions: We find potent MPXV-specific IFN-g responses in MPXV-R and -V individuals. In PLWH who recovered from Mpox, we observed elevated IFN-g responses which suggests immune imprinting. The etiology of low GB responses in MPXV-R and -V is unclear but could suggest loss of circulating effector cytotoxic T cell responses after recovery of Mpox or vaccination. Further epitope characterization of these peptides will inform future MPXV vaccines. Immune Response After 2 Years From MVA-BN Vaccination by HIV Infection and CD4 Cell Count Valentina Mazzotta, Giulia Matusali, Elelonora Cimini, Francesca Colavita, Jessica Paulicelli, Rozenn Esvan, Aurora Bettini, Alessandra Oliva, Flavia Cristofanelli, Giulia Micheli, Eleonora Tartaglia, Alessandro Caioli, Enrico Girardi, Fabrizio Maggi, Andrea Antinori IRCCS Lazzaro Spallanzani, Rome, Italy Background: The current mpox resurgence raised the question of the residual immune protection conferred by the MVA-BN vaccination received during the 2022 outbreak. Available data on long-term immune response after MVA-BN are scarce, especially in PWH with low CD4 count, who are at high risk of severe and prolonged mpox and a possible impaired vaccine immune response. We described humoral, and T-cell immune responses elicited up to two years from MVA-BN vaccination, stratifying results according to HIV infection and CD4 count to provide elements to establish the need for a vaccine boost. Methods: Blood samples from people receiving a primary two-dose course of MVA-BN were prospectively collected at the time of each dose administration (T1-T2) and then after 1 (T3), 6 (T4), 12 (T5) and 24 (T6) months. Neutralizing antibodies (nAbs) were assessed by a 50% plaque reduction neutralization test and interferon-γ producing MVA-BN specific T-cells by ELISpot assay. Data at T6 were stratified according to HIV infection and CD4 count (<350 and >350). Kruskal-Wallis with Dunn tests, Wilcoxon, and Mann-Whitney tests were used for statistics. Results: All the 40 people enrolled were MSM, not primed for smallpox during childhood, with a median age of 41.5 years (IQR 35-45). Among the 20 (50%) PWH, 9 (45%) had a CD4 count <350 mmc. After peaking one month from vaccination, nAb titers progressively dropped in the following time points, with less than 25% of sera reactive at two years (T6). The MVA-BN-specific T-cell response raised early after vaccination, remained stable until one year, and significantly decreased at two years (p=0.02). At that time, no evidence for a difference was detected between PWoH and PWH with CD4 count <350 or >350, both for cellular and neutralizing response. Conclusions: Two years after receiving MVA-BN, regardless of HIV infection and CD4 count, a poor neutralizing response was detected, while T-cell response persisted despite being substantially diminished. A booster MVA-BN dose at least two years after the primary cycle seems necessary both to reactivate the humoral response and recall the residual cellular response, accounting for most of the clinical protection observed so far. The figure, table, or graphic for this abstract has been removed. RV550: IL-15 Superagonist N-803 With ART in Acute HIV Infection Enhances T and NK Cell Proliferation Hiroshi Takata 1 , Julian Pacheco 1 , Suteeraporn Pinyakorn 2 , Carlo Sacdalan 3 , Pathariya Promsena 3 , Somchai Sriplienchan 3 , Kiat Ruxrungtham 4 , Morgane Rolland 2 , Jeffrey Safrit 5 , Bobby Reddy 5 , Sandhya Vasan 6 , Lydie Trautmann 6 , Afam Okoye 1 , for the RV550 and RV254/SEARCH010 Study Groups 1 Oregon Health and Science University, Portland, OR, USA, 2 US Military HIV Research Program, Bethesda, MD, USA, 3 SEARCH, Bangkok, Thailand, 4 Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 5 ImmunityBio, San Diego, CA, USA, 6 Henry M Jackson Foundation, Bethesda, MD, USA Background: In the RV550 clinical trial, we hypothesized that IL-15 superagonist N-803 administration with ART during acute HIV infection (AHI) would limit HIV reservoir establishment and persistence. Here, we characterized the effects of N-803 on T cells and NK cells in peripheral blood (PBMC) and lymph nodes (LN). Methods: Participants with AHI (Fiebig I-IV) were randomized in an open-label manner to receive N-803 (6ug/kg) subcutaneously at weeks 0, 3, and 6 post-ART (n=10) or no N-804 (n=4), with LN biopsies obtained at week 0 and 4 days after week 6. Immune cell dynamics in PBMC and LN were assessed by flow

cytometry. Differences between groups were analyzed by Mann-Whitney U tests. Results: N-803 induced proliferative expansion of T cells and NK cells, with a significant increase in Ki-67 + CD8 + T cells ( Figure 1A ) and Ki-67 + NK cells observed after the 2nd dose (p=0.003 and p=0.003, respectively) in PBMC, and after the 3rd dose in PBMC (p=0.004 and p=0.004, respectively) and in LN (p=0.006 and p=0.03, respectively) of participants who received N-803 + ART compared to ART alone. Perforin expression in Ki-67 + CD8 + T cells after the 1st and 2nd dose (p=0.01 and p=0.03, respectively) and EOMES expression in NK cells after the 1st, 2nd and 3rd dose (p=0.04, p=0.03, and p=0.02, respectively) in PBMC were also increased with N-803 treatment. N-803 also increased Ki-67 + CD4 + T cells after the 1st, 2nd and 3rd dose in PBMC (p=0.008, p=0.003, and p=0.002, respectively) and in LN (p=0.004) after the 3rd dose. Finally, we observed increased expression of the anti-apoptotic molecule BCL-2 in proliferating CD4 + T cells in PBMC after the 2nd (p=0.02) and 3rd dose (p=0.048) of N-820 (Figure 1B). Despite these effects, plasma viral loads were comparable between N-803-treated participants and controls. Conclusions: N-803 induced the proliferation and effector differentiation of CD8 + T cells and NK cells, suggesting it may be effective at enhancing the cytolytic activity of antiviral lymphocytes. The effects of this on HIV reservoir dynamics is under evaluation. DISCLAIMER: The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, the National Institutes of Health, the Department of Health and Human Services, or the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The investigators have adhered to the policies for protection of human subjects as prescribed in AR-70-25. NF-kappa-B Signaling in Natural Killer Cells Predicts Post-Treatment HIV Control Ashley F. George 1 , Tongcui Ma 1 , Natalie Elphick 1 , Kyrlia C. Young 1 , Reuben Thomas 1 , Julie Frouard 1 , Antonio Rodriguez 2 , Tony R. Figueroa 2 , Meghann Williams 2 , Rebecca Hoh 2 , Jonathan Li 3 , Katherine S. Pollard 1 , Steven G. Deeks 2 , Michael Peluso 2 , Nadia R. Roan 1 1 Gladstone Institutes, San Francisco, CA, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 Brigham and Women's Hospital, Boston, MA, USA Background: For most people with HIV (PWH) on antiretroviral therapy (ART), cessation of ART results in rapid rebound of viremia. However, in rare individuals, called post-treatment controllers (PTCs), HIV is controlled through poorly understood mechanisms. The objective of this study was to leverage multiomics single-cell sequencing approaches to assess the extent to which the transcriptomic and epigenetic features of immune cells in PTCs differ between those non-controllers (NCs). Methods: A total of 6 PTCs and 7 NCs were identified from the UCSF OPTIONS cohort. PTCs were defined as PWH who upon ART interruption maintained viral loads ≤400 copies/mL for at least two-thirds of the time points while off ART for ≥24 weeks. NCs, by contrast, were defined as PWH who upon ART interruption experienced viral rebound to viral loads exceeding 400 copies/mL within 24 weeks. We performed multiomics single-cell assay for transposase-accessible chromatin (scATAC) and single-cell RNA (scRNA) sequencing on PBMCs collected from these individuals immediately prior to their undergoing treatment interruption. As prior evidence suggests that Natural Killer (NK) cells influence the timing of viral rebound, our analysis specifically focused on these cells. Results: Analysis of scRNA-seq data revealed 447 genes that were differentially expressed (p<0.05; |log2(fold change)|>0.5) in NK cells from PTCs compared to NCs. Genes involved in the NF-kappa-B signaling pathway, including NFKB1 and RELB , were significantly elevated (p<0.05; |log2(fold change)|>0.5) in NK

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