CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

440

Immune Response to Mpox in PWH and PrEP Users After Infection, but Not in Response to Vaccination Olivia de la Calle-Jiménez 1 , Guiomar Casado Fernández 1 , Inés Armenteros Yeguas 2 , Luis Fernando Lemus Aguilar 1 , Jorge Pérez-García 2 , Javier Rodríguez Añover 3 , Elena Mateos 1 , Reynaldo Homen 3 , Noemí Cabello-Clotet 3 , Anabel Negredo 1 , María Paz Sánchez Seco 1 , Jorge Del Romero 4 , Vicente Estrada 3 , Montserrat Torres 1 , Mayte Coiras 1 1 Instituto de Salud Carlos III, Madrid, Spain, 2 Centro Sanitario Sandoval, Madrid, Spain, 3 Hospital Universitario Clínico San Carlos, Madrid, Spain, 4 Centro Sandoval, Madrid, Spain Background: In May 2022, WHO considered the outbreak of mpox infection as a public health emergency of international concern (PHEIC). Vaccination was recommended for people living with HIV (PWH) and users of pre-exposure prophylaxis (PrEP). The need to vaccinate the population at risk worldwide, mainly PWH and PrEP users has increased. The immune response generated after infection was analyzed in comparison with vaccinated individuals. Methods: We recruited mpox-infected persons (mpox+)(n=31), mpox vaccinated persons (n=13;n=11 one and two doses) and persons who were not in contact with mpox and smallpox (non-exposed)(n=38). Mpox peptides were used to stimulate CD4+ and CD8+ T cells and the expression of different markers and cytokines was analyzed by flow cytometry. Results: 1)The mpox+ participants were infected a median of 258(IQR 254-285) days ago; those vaccinated with one dose a median of 339 days ago(IQR 288-349) and those who received two doses 126(IQR 72-169) days ago. The median age of the groups was 37(IQR 34-47), 34(IQR 32-40), 38(IQR 35-41) and 34(IQR 27-46) years respectively. All participants were male. There were 25 PWH mpox+(80.6%), 4 PWH vaccinated(32.2%) and 11 PWH in the non exposed group (28.9%). 2)CD4+ T-cell stimulation induced a 1.5(p=0.0128) and 1.3(p=0.0486) fold decrease in lymphocyte levels in the mpox+ group compared to single dose vaccinated and non-exposed group. CD4 lymphocytes expressed 1.8(p=0.0439) times higher levels of IL-2 in mpox+ individuals compared to those vaccinated with two doses. 3)Naive CD4+ T cells in the mpox+ group expressed higher levels of CD25+ marker (1.5-fold;p=0.0155) compared to the non-exposed group and of IFNγ (2.5-fold; p=0.0265) compared to those vaccinated with two doses. 4)Central memory CD4+ CD4+ T cells were increased 3.1 (p=0.0118) and 2-fold (p=0.0183) more in mpox+ individuals compared to those vaccinated with two doses and the non-exposed group, respectively. 5)CD8+ T cells expressed 1.6 (p=0.0321) and 2.1 (p=0.0084) times more IFNγ and TNFα than those vaccinated with one dose respectively. 6)No difference was found between the response of HIV-infected and PrEP users. Conclusions: People infected with mpox showed a potent and long-lasting immune response to mpox peptides. Vaccination against mpox did not produce significant changes in the capacity to response to mpox peptides compared to those not previously exposed to the virus. MVA Vaccine Produces Potent Serological and Immunological Response to Mpox in People With HIV Maryam Khan 1 , Scott Jones 2 , Hafiza Rahman 3 , Helena Miras 3 , Ashley Otter 2 , John Thornhill 1 , Neil McCarthy 1 , Krishanthi Subramaniam 4 , Chloe Orkin 1 , for the SHARE Collaborative 1 Queen Mary University of London, London, UK, 2 UK Health Security Agency, London, UK, 3 Barts Health NHS Trust, London, UK, 4 University of Liverpool, Liverpool, UK Background: People living with HIV (PLWH) comprised a large proportion of those who acquired mpox during the global outbreak. The predominant control strategy for mpox is the use of modified vaccinia virus Ankara (MVA), a smallpox vaccine. However, the efficacy and durability of this vaccine in PLWH is unclear. We investigated immune responses in PLWH with past mpox infection and those vaccinated with two doses of MVA to better understand mpox immunity in context of HIV. Methods: Study participants were PLWH, male, virally suppressed (VL<50 c/ mL) on ART with no evidence of immunosuppression (median CD4:931, IQR:394 892, CD8:515, IQR:393-892). Plasma and PBMC samples from past-infection (PI) cohort (n=9, median age= 42, IQR=36-47) and vaccination (Vax) cohort (n=8, median age =41, IQR=41-53) were taken at single time-point at least three months post-infection or post-vaccination. IgG responses to 9 mpox (MPXV) recombinant antigens (A5L, A27L, A29L, A35R, B2R, B6R, E8L, H3L, M1R) and 3 Vaccinia virus (VACV) (VA27L, VA33R, VB5R) were measured using Luminex and reported as mean fluorescent intensity (MFI). IFN-γ CD4+ and CD8+ T-cell responses were measured in response to pools of MPXV-specific

and orthopoxvirus (OP)-specific peptides using ELISPOT and reported as spot forming units (SFU)/10 6 PBMCs. Results: 15/17 participants produced potent serological responses to MPXV and VACV antigens. No difference in serological responses was observed for 8 MPXV antigens 3 VACV antigens between PI and Vax cohorts (p=0.6). MFI for A27L (median, 95%CI), an infection-specific antigen was significantly higher (p=<0.05) in PI (2819,1754-4537) compared to Vax (133,823-1230). Notably, two PLWH in Vax cohort produced no detectable IgG to any antigens, however, both produced potent OP T-cell responses. Overall, CD4+ and CD8+ T-cell responses (median, 95%CI) to OP peptides were significantly higher (p=<0.05) in Vax cohort (46,13-200) compared to PI cohort (22,13-54) ( Fig1 ). MPXV T-cell responses were comparable in PI and Vax cohorts (p=0.07). Conclusions: MVA vaccination and mpox infection produced potent serological responses in PWH. MVA resulted in higher CD4+ and CD8+ T-cell responses to OP peptides in the Vax cohort which has important public health implications on how vaccines should be prioritised. These findings also highlight the importance of monitoring how these responses are sustained in PLWH. This work is relevant to an immunocompetent virally suppressed cohort with no evidence of immune activation.

Poster Abstracts

442

Mpox-Specific T-Cell Responses in Recovered and Vaccinated Individuals Aideen S. Teeling 1 , Thomas C. Morningstar 1 , Antonio Estacio 2 , Feng Yun Yue 1 , Megan Buchholz 2 , Katerina Pavenski 2 , Patti Lou Cheatley 2 , Darrell H. S. Tan 2 , Annam Imran 1 , Suji Udayakumar 1 , Joseph De Fazio 1 , Mutian Wang 1 , Mario Ostrowski 1 1 University of Toronto, Toronto, Canada, 2 St Michael's Hospital, Toronto, Canada Background: In 2022, Clade IIb human monkeypox virus (MPXV) led to Mpox outbreaks in many non-endemic countries. Modified vaccinia Ankara vaccines (Imvamune®) are used to curb MPXV transmission. However, vaccine effectiveness is limited and Mpox immunity is not well characterized, especially in persons living with HIV (PLWH). We hypothesized that T cell responses to MPXV antigens produced early in infection may be effective in immune clearance. Methods: Using the Immune Epitope Database, we created a panel of 46 peptides derived from proteins produced early in poxvirus infection also present in MPXV Clade IIb. 28 male participants from Toronto, Canada (mean age = 41 years; range = 21-75) were enrolled: 15 (53%) were PLWH all on anti-retroviral therapy (ART), 10 individuals recovered from Mpox (MPXV-R; median = 376 days post symptom onset), 9 received two doses of Imvamune® (MPXV-V; median time since second dose = 5 mo), and 9 were poxvirus-naïve individuals (MPXV N). Peptide specific interferon gamma (IFN-g) and granzyme B (GB) responses were determined using ex vivo peripheral blood mononuclear cells (PBMC) by enzyme-linked immunosorbent spot assays in spot-forming cells per million PBMC (SFC/106 PBMC). Peptide responses were considered positive if SFC/10 6 PBMC were at least twice the average MPXV-N response and ≥ 20. We compared responses among MPXV-R, -V, and -N groups using Kruskal-Wallis tests, and HIV status with Mann-Whitney U tests. Results: 18/19 (95%) of MPXV-R and MPXV-V participants responded to at least 3 peptides, with IFN-g responses being more frequent than GB. The median total IFN-g responses using our peptides were 1794 vs 1078 vs 328 SFC/10 6 PBMC in MPXV-R, MPXV-V, MPXV-N, respectively (p<0.01). IFN-g responses tended to be greater in PLWH than people without HIV in MPXV-R (median = 2389 vs. 389 SFC/106 PBMC, p=0.067). Total GB responses were much lower than IFN-g responses (e.g. MPXV-R median = 185 SFC/10 6 PBMC) and significant

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