CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

A non-significant increase of IFNγ CD8 T-cell responses was detected against the B.1.351 variant. No increases in IL-2-producing CD4 and CD8 T cells were observed. Conclusions: PHH-1V vaccine elicits a robust IFNγ T cell response in healthy pediatric adolescents when administered as a heterologous boost. Our findings are similar to those obtained in the heterologous boost study with healthy adults aged 18 to 65 years old (HIPRA HH-2). Noteworthy, the present study indicates a more pronounced IFNγ T cell immune response in adolescents than adults, potentially reflecting their maturating immune system. T-Cell Immunity of PHH-1V COVID-19 Vaccine in PWH and Adults With Immunosuppressive Conditions Raúl Pérez-Caballero 1 , Ignasi Esteban 2 , Laia Bernad 1 , Elena Aurrecoechea 3 , Yovaninna Alarcón-Soto 4 , Ruth Peña 1 , Susana Benet 4 , Jorge Carrillo 1 , Nuria Izquierdo-Useros 1 , Julià Blanco 1 , Laura Ferrer 5 , Beatriz Mothe 4 , Montserrat Plana 3 , Julia G. Prado 1 , for the RBDCOV Study Group 1 IrsiCaixa, Badalona, Spain, 2 Hospital Clinic of Barcelona, Barcelona, Spain, 3 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 4 Fundació Lluita contra la SIDA, Badalona, Spain, 5 HIPRA, Girona, Spain Background: Protective vaccines became an urgent need during the COVID-19 pandemic. People with immunodeficiencies particularly benefit from COVID-19 vaccination. PHH-1V (BIMERVAX®) is an authorized and adjuvanted recombinant vaccine based on a dimeric RBD of Alpha/Beta SARS-CoV-2 variants. HH-4 was a Phase IIb/III, open-label, single-arm, multi-center study (NCT05303402) to evaluate the humoral and cellular immune response elicited by PHH-1V booster in people with HIV-1 (PHW) and other immunodeficiencies considered to be at higher risk of adverse COVID-19 outcomes compared to the general population. Here, we evaluate cellular immune responses elicited by the PHH-1V booster in individuals with 5 different immunosuppressive conditions. Methods: We analyzed the cellular immune responses after PHH-1V booster vaccination in cryopreserved PBMC samples at baseline (D0) and day 14 after vaccination (D14) in 5 immunosuppressed groups: people with HIV (PWH, n=30), kidney transplant (KTx, n=23), kidney disease on hemodialysis (HD, n=26), primary antibody deficiency disorders (PAD, n=18), and auto-immune disease on treatment with rituximab/ocrelizumab (AID, n=44). We measured total magnitude of T-cell responses and functionality by IFN-γ ELISpot and intracellular staining (ICS) assays, respectively, using 15-mer overlapping RBD 84-peptide pools of Omicron BA.1 and BA.2, Wuhan, B.1.351 (Beta, vaccine matched) and B.1.617.2 (Delta). Mixed effects models were used on squared root transformed data stratified by sex. Results: Total T-cell responses assessed by ELISpot significantly increased (p<0.05) in all the study groups, except for KTx, against the different SARS-CoV 2 pools. T-cell responses against Delta and Wuhan RBD pools were only found in PAD, PWH and AID groups, respectively. T-cell functionality also demonstrated a significant increase in IFN-γ secretion against SARS-CoV-2 peptides on CD4 + T-cells (RBD Omicron BA.1 in PWH and HD; RBD Omicron BA.2 in HD and PAD; RBD Beta in PWH and KTx, RBD Delta in AID; RBD Wuhan in PWH, HD and AID). Significant increases were observed in IL-2-producing CD4 + (RBD Omicron BA.2 in PAD) and in CD8 + T-cells (RBD Omicron BA.2 in HD and RBD Beta in PWH). Conclusions: PHH-1V booster vaccination boosts cellular immunity against SARS-CoV-2 in PWH and a broad range of individuals with immunosuppressive conditions expanding specific IFN-γ + CD4 + T-cell phenotype across groups. The level of T-cell responses varies according to the underlying condition and/or its associated treatment. Torque Teno Virus: A Predictive Biomarker for SARS-CoV-2 Vaccine Response in Immunosuppressed People Gonzalo Cabrerizo 1 , Nicolás Ducasa 1 , Cecilia Monzani 1 , Paula Benencio 2 , Ezequiel Mauro 3 , Fernando Cairo 4 , Milagros Acevedo 1 , Denise Giannone 1 , María Belén Vecchione 1 , Federico Remes Lenicov 1 , Manuel Barbero 4 , Margarita Anders 5 , Manuel Mendizabal 6 , Maria Florencia F. Quiroga 1 , Mirna Biglione 1 1 Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Buenos Aires, Argentina, 2 University of Buenos Aires, Buenos Aires, Argentina, 3 Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 4 Hospital El Cruce, Buenos Aires, Argentina, 5 Hospital Alemán, Buenos Aires, Argentina, 6 Hospital Universitario Austral, Buenos Aires, Argentina Background: Solid organ transplant recipients (SOTRs) are highly susceptible to severe COVID-19 due to chronic immunosuppressive treatment aimed at preventing organ rejection, along with associated comorbidities. Their vaccine responses are often diminished compared to the general population. Identifying a biomarker that reflects immune status and predicts vaccination response

is crucial for optimizing vaccination strategies. Torque Teno virus (TTV), a component of the human virome, has previously been identified as a marker of immune competence. Our objective was to develop an in-house qPCR assay to measure TTV viral load and evaluate its potential as a predictor of humoral response to SARS-CoV-2 vaccination. Methods: We designed TTV-specific primers, optimized a Sybr Green qPCR, and created a standard using a topo cloning vector containing TTV isolated from a liver transplant recipient (LTR), which was subsequently sequenced for validation. We determined TTV viral load in plasma samples from LTRs and healthy donors (HD) after administering the initial vaccination regimen (first and second doses) and the booster dose (third dose) of the SARS-CoV-2 vaccine. The humoral response included the measurement of anti-Spike antibodies and neutralizing antibodies. Results: The prevalence of TTV in LTRs was 91.4% (70/77), compared to 92.9% (13/14) observed in HD. LTRs exhibited a significantly higher TTV viral load after the initial vaccination regimen (median log10(copies/mL): 5.50) compared to HD (median log10(copies/mL): 4.10) (p=0.0001). Among LTRs, those who failed to develop a humoral response had a higher TTV viral load (median log10(copies/ mL): 5.94) than those with a successful response (median log10(copies/ mL): 4.59) (p<0.0001). This trend persisted after the booster dose, with LTRs showing a median TTV viral load of 5.76 compared to HD at 4.39 (p=0.0027). Non-responders exhibited an even higher TTV viral load (median log10(copies/ mL): 5.95) compared to responders (median log10(copies/mL): 5.53) (p=0.004). Notably, there was a correlation between total anti-spike IgG antibody levels in plasma and TTV viral load (p<0.05) in LTRs, both after the initial vaccination regimen and following the booster dose. Conclusions: In conclusion, a high TTV viral load predicts a poor humoral response to SARS-CoV-2 vaccination. This biomarker should continue to be investigated as a predictor of overall immune status. Limited Effectiveness of High-Dose Flu Vaccine in Augmenting Immunity in Older People With HIV Jonah Kupritz, Sheldon Davis, Prabhsimran Singh, Tianhao Liu, Daniel Diaz Pachón, Allan Rodriguez, Rajendra Pahwa, Savita Pahwa, Suresh Pallikkuth, for the Miami Center for AIDS Research University of Miami, Miami, FL, USA Background: Chronologic aging has been reported to impair antibody responses to influenza (flu) vaccination with greater impairment in PWH occurring at a younger age than in people without HIV (PWoH). High-dose (HD) vaccine, with four times more antigen than standard-dose (SD), is recommended for people ages ≥65 years to improve effectiveness but has not been widely studied in PWH. Methods: 237 participants (PWH, virally suppressed, and PWoH) consisting of young (Y, 18-40 years; PWH, N =42 and PWoH, N =56) and old, (O, ≥60 years; PWH, N =67 and PWoH, N =72) were enrolled into the study (NCT04487041) and given SD vaccine during the 20-21, 21-22, or 22-23 flu seasons. The following season, HD vaccine was given to a subset of participants (OPWH: N =37; OPWoH: N =37; YPWH: N =15; YPWoH: N =18). Serum hemagglutination inhibition (HAI) titers to H1N1 (H1), H3N2 (H3), B/Yamagata (B Yam ), and B/Victoria (B Vic ) antigens were measured at 0-, 28-, and 180-days post-vaccination (dpv). As recent H3 viruses do not bind red blood cells, we could not assess H3 HAI responses to HD. Nonparametric tests and linear regression were performed in R . P values <0.05 were deemed significant. Results: Baseline titers did not differ between PWH and PWoH but compared to Y, O had lower H3 (1:65 vs. 1:110, P <0.01) and B Vic (1:100 vs. 1:134, P <0.01), higher B Yam (1:58 vs. 1:45, P <0.05), and similar H1 titers. At 28 dpv-SD, although H1, H3, and B Yam titers increased more than two-fold from baseline in all groups, log2 fold-change (FC) from 0 dpv to H1 was lower in O than in Y (1.7 vs. 2.3, P <0.05). Moreover, H1 titers (1:298 vs.1:425, P <0.01) and FC (1.7 vs. 2.1, P =0.06) were lower in PWH than in PWoH. After HD, at 28 dpv, H1 titers remained lower in O (1:306 vs. 1:430, P <0.05) and PWH (1:279 vs. 1:401, P =0.07) compared to Y and PWoH. On paired analysis at 28 dpv-HD, H1 titers did not differ from SD in OPWH (Table 1) and, unexpectedly, decreased in PWoH (1:504 vs. 1:341, P <0.05). At 180 dpv-HD, titers for all antigens dropped significantly from 28 dpv levels and no longer differed from the baseline, for all groups. In a regression model which controlled for age, race, HIV status, and vaccination history, HD was associated with improvements only in 28 dpv B Vic responses (β=757, P <0.05).

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CROI 2025 120

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