CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

neurocognitive or gastrointestinal symptoms (P=0.037, P=0.04, respectively). Overall, the percentage of CD56dim/CD16+ NK cells negatively correlated with the number of LC symptoms (Spearman r=-0.5, P=0.022). Compared to those who recovered, participants with severe LC also had lower percentages of CD56dim NK cells expressing KIR2D(L1/S1/S3/S5) (23.7% vs 16.1%; P=0.036). In multidimensional analyses, we did not find significant differences in NK cell UMAP clusters with adaptive NK cell features, as have been described in acute COVD-19, between those with and without LC. However, we did observe a significant increase in percentage of adaptive NK clusters in CMV IgG+ participants versus IgG- participants (P=0.024). Conclusions: We observed a lower percentage of NK cells of the canonical mature, cytotoxic phenotype in people with LC compared to those who recovered. Reduced cytotoxic killing and impaired clearance of SARS-CoV-2 infected cells could be related to the development of LC. Alternatively, these data could suggest chronic tissue redistribution in response to persistent viral triggers in people with LC. The XBB.1.5 mRNA Booster Vaccine Does Not Significantly Increase XBB.1.5 Mono-Reactive T Cells Joel Sop, Alicia Mercado, Alexis Figueroa, Tyler Beckey, Caroline Traut, Li Zhang, Kellie Smith, Joel Blankson The Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: SARS-CoV-2 variants such as XBB.1.5 and BA.2.86 have emerged with mutations that allow them to evade neutralizing antibodies elicited by ancestral and bivalent mRNA vaccines. Despite the introduction of the XBB.1.5 monovalent booster to improve T cell immunity, it remains unclear whether this vaccine induces stronger XBB.1.5-specific T cell responses compared to the ancestral/BA.5 bivalent vaccines. We hypothesized that the XBB.1.5 booster would significantly increase the percentage of XBB.1.5 mono-reactive T cells. Methods: We used the IFN-gamma ELISpot assay to determine the targeted epitopes and the functional expansion of specific T cells (FEST) assay to assess the percentage of CD4+ T cells that cross-recognized ancestral, BA.5, and XBB.1.5 spike proteins versus those that were mono-reactive. The FEST assay involves culturing antigen-specific T cells with spike peptides, followed by TCR sequencing to identify expanded clonotypes. 11 participants who received either the ancestral/BA.5 bivalent mRNA vaccine or the XBB.1.5 monovalent mRNA booster vaccine were included in the study. Results: Our analysis revealed robust T cell responses to ancestral, BA.5, and XBB.1.5 spike proteins. However, the XBB.1.5 booster did not significantly increase the percentage of XBB.1.5 mono-reactive T cells. The percentage of spike-specific CD4+ T cell receptors that were XBB.1.5 mono-reactive did not increase significantly after the booster shot (7.6% pre-booster to 12.3% post-booster, p=0.4375). Instead, cross-reactive CD4+ T cells dominated the spike-specific T cell response. Furthermore, the percentage of T cell-targeted epitopes containing XBB.1.5 mutations did not significantly change after the booster (27.9% pre-booster to 23.75% post-booster, p= 0.6667). Conclusions: Our findings suggest that the XBB.1.5 monovalent booster does not substantially enhance XBB.1.5-specific T cell responses, with cross reactive T cells continuing to dominate the immune response. These results have important implications for future vaccine strategies targeting emerging variants. Evaluation of Salivary Antibody in Protection From SARS-CoV-2 Infection Sharon Walmsley 1 , Majid Nabipoor 1 , Gary Chao 2 , Lesley Ward 2 , Rizani Ravindran 1 , Erik Lovblom 1 , Jennifer Gommerman 2 , for the STOPCoV Research Team 1 University Health Network, Toronto, Canada, 2 University of Toronto, Toronto, Canada Background: The primary route of infection for SARS Cov-2 is through inhalation. The virus can infect cells along the mucosal tract from nares and mouth to gut. The impact of the mucosal immune response in control of the infection and protection from reinfection unclear. It is unknown whether a nasal vaccine would provide better protection. Our objective was to determine the IgG and IgA antibody levels in the saliva of a subset of persons participating in a longitudinal observational study of COVID immunity and to compare responses in those with vaccine only and those with hybrid immunity. Methods: A random sample of 180 persons participating in the STOPCoV study (n=1286, mean follow up 1.5 years, mean 5 vaccine doses) were invited to participate in a sub-study of mucosal immunity. Samples of saliva were collected in December 2022 and April 2023. We analyzed the levels of IgG and IgA to spike protein and receptor binding domain (RBD) to the Wuhan

ancestral strain and Omicron variant in 51 participants. We excluded individuals who had a breakthrough infection or received a vaccine dose in the interval between testing periods. We selected those with hybrid immunity who had a breakthrough infection in the previous 6 months. Regression for continuous outcomes (antibody levels) and survival outcomes (subsequent breakthrough infection) was used. Results: Participants with hybrid immunity were more likely to have detectable IgA antibody to RBD than those with vaccine only immunity to both the Wuhan ancestral strain (100%, 79%) p=.04 and the Omicron variant (93%, 74%) p=.11. Similar trends were seen with IgA antibody to spike to Wuhan (94%, 82%) p=.24 and all has positive IgA antibody to spike to Omicron . Significant decay was seen with IgA antibody to RBD protein to both Wuhan and Omicron between the two sampling periods. Neither salivary IgA positivity nor the relative level of IgA antibody to Omicron was predictive of protection from breakthrough infection over the subsequent year, although receipt of an additional COVID vaccine was. Conclusions: Hybrid immunity was associated with higher proportions of individuals having positive mucosal IgA and IgG antibodies to spike and RBD proteins of SARSCo -2 but these decayed with time and were not associated with protection from a breakthrough infection in the following year.

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Evaluation of the PHH-1V COVID-19 Vaccine Induced T-Cell Responses in Adolescents: HIPRA-HH-3 Study Ignasi Esteban 1 , Raúl Pérez-Caballero 2 , Elena Aurrecoechea 3 , Roc Pomarol 1 , Laia Bernad 2 , Ruth Peña 2 , Manuel Cañete 4 , Antoni Prenafeta 4 , Laura Ferrer 5 , Pere Soler-Palacín 6 , Borja Guarch 7 , Silvina Natalini Martínez 8 , Julia G. Prado 2 , Montserrat Plana 3 , for the RBDCOV Study Group 1 Hospital Clinic of Barcelona, Barcelona, Spain, 2 IrsiCaixa, Badalona, Spain, 3 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, 4 HIPRA, Amer, Spain, 5 HIPRA, Girona, Spain, 6 Hospital Universitari Vall d'Hebron, Barcelona, Spain, 7 Hospital Universitari Dr Josep Trueta, Girona, Spain 8 Background: PHH-1V (BIMERVAX®) is an adjuvanted recombinant protein vaccine based on a dimeric RBD of the Alpha/Beta SARS-CoV-2 variants. In March 2023 PHH-1V received full marketing approval by EMA (European Medicines Agency) to be used as a heterologous booster for preventing coronavirus disease 2019 (COVID-19) in people aged 16 and older. The HH-3 study (Phase IIb, Open label, Multi-center, Non-Inferiority, NCT06234956) aims to assess the safety and immunogenicity of PHH-1V in 300 healthy adolescents (pediatric population), with ages comprised 12 to 17 years, that had been previously vaccinated with mRNA-based SARS-CoV-2 vaccines. Here, we evaluate the T-cell immune response in a group of 16 study participants. Methods: Cryopreserved peripheral blood mononuclear cells (PBMC) samples were obtained from participants (n=16) on baseline (D0) and day 14 (D14) after receiving the PHH-1V booster. PBMCs were isolated and stimulated with 15-mer overlapping peptides pools (84 peptides) covering the RBD region of the Spike protein from the RBD Omicron BA.1 and RBD B.1.351 (Beta) variants of the SARS CoV-2 virus. T-cell responses were evaluated using ELISpot and Intracellular Cytokine Staining (ICS) techniques. We measured the magnitude of IFNγ T-cell responses by ELISpot assay (Spot Forming Units, SFU per million) after a 24-hour peptide stimulation. ICS measured percentages of IFNγ, IL-2 and IL-4 secreting CD4 and CD8 T-cells after 6 hours of peptide stimulation. Results: ELISpot assay showed a significant increase in IFNγ-producing T cells at D14 after vaccination with both RBD peptide pools tested (RBD B.1.351 p<0.0001, RBD Omicron BA.1 p<0.0001). ICS assay demonstrated that most of the IFNγ secreting cells have a CD4+ T-cell phenotype (RBD B.1.351 p<0.0001, RBD Omicron BA.1 p=0.0002), although an increase of IL-4 secreting CD4+ T-cells was detected against peptides from the B.1.351 variant (p=0.0381).

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