Biology subjects

Samaan, P.

Publications and source records attributed to Samaan, P..

4 recordsLinked to original sources

bioRxiv2026

Diminished EBV-Specific Humoral Immunity is Associated with Neuropsychiatric Long COVID Development up to 12 Months Post-COVID-19 Symptom Onset

Infection with SARS-CoV-2 can lead to long COVID, a chronic multisystemic condition estimated to affect approximately 400 million people worldwide. Although underlying mechanisms remain elusive, aberrant ongoing inflammation driven by Epstein-Barr virus (EBV) reactivation and persistent SARS-CoV-2 viral reservoirs have been hypothesized. We compared cellular and humoral immune responses to SARS-CoV-2 and EBV between participants with neuropsychiatric long COVID and recovered individuals. Peripheral blood mononuclear cells (PBMCs) and sera were collected from 27 long COVID individuals with [≥]2 neuropsychiatric symptoms and 27 matched recovered participants at 3-6 months post-COVID-19 symptom onset (PSO). PBMCs were assessed for IFN-{gamma}, IL-2, TNF, and granzyme B T-cell responses against SARS-CoV-2, EBV, and human cytomegalovirus (HCMV). Sera were evaluated for neutralizing activity against live ancestral SARS-CoV-2 and EBV, and EBV reactivation was assessed by early antigen-diffuse IgG. We observed no significant differences in SARS-CoV-2-, EBV-, or HCMV-specific T-cell responses or live virus neutralization between long COVID and recovered groups at 3-6 months PSO. EBV reactivation was additionally only detected in one neuropsychiatric long COVID participant. However, reduced EBV neutralizing capacity at 3-6 months significantly associated with fatigue at 12 months PSO. Anti-EBV viral capsid antigen IgG levels were also significantly diminished in long COVID participants and similarly trended lower in those reporting fatigue at 12 months PSO. We therefore detected no differences in SARS-CoV-2- or EBV-specific T-cell responses or serological neutralizing capacity between neuropsychiatric long COVID and recovered participants; however, diminished EBV-specific humoral immunity may serve as a prognostic marker for neuropsychiatric long COVID development. IMPORTANCEWe performed a comprehensive analysis of cellular and humoral immune responses to SARS-CoV-2, Epstein-Barr virus, and human cytomegalovirus in individuals with neuropsychiatric long COVID, a subgroup that remains poorly characterized. Although no differences in virus-specific T-cell immunity were observed between long COVID and recovered individuals, diminished Epstein-Barr virus neutralization at 3-6 months was associated with persistent or relapsing fatigue at 12 months post-COVID-19 symptom onset. Anti-viral capsid antigen IgG antibody levels were also significantly lower in neuropsychiatric long COVID participants at 3-6 months and similarly trended lower in those reporting fatigue at 12 months post-symptom onset. Together, these findings suggest that impaired humoral immunity to Epstein-Barr virus may contribute to the development or persistence of neuropsychiatric long COVID and highlight a promising future direction for mechanistic studies.

immunology↗

bioRxiv2024

mRNA Vaccine-Induced SARS-CoV-2 Spike-Specific IFN-γ and IL-2 T-cell Responses are Predictive of Serological Neutralization and are Transiently Enhanced by Pre-Existing Cross-Reactive Immunity

The contributions of SARS-CoV-2-specific T-cells to vaccine efficacy and durability are unclear. We investigated the relationships between mRNA vaccine-induced spike-specific IFN-{gamma} and IL-2 T-cell responses, anti-spike/RBD IgG/IgA antibodies, and live virus neutralizing capacity in long-term-care-home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity to SARS-CoV-2 on cellular and humoral responses to vaccination were additionally assessed. Mathematical modelling of the kinetics of spike-specific IFN-{gamma} and IL-2 T-cell responses over 6-months post-second dose was bifurcated into recipients who exhibited gradual increases (54% and 42%, respectively) with doubling times of 173 days, or decreases (46% and 58%, respectively) with half-lives of 115 days. Differences in kinetics did not correlate with any clinical phenotypes, although increases were proposed to be due to subclinical viral exposures. Serological anti-spike/RBD IgG/IgA antibody levels had otherwise decayed in all participants with half-lives of 55, 53, 76, and 59 days, respectively. Spike-specific T-cell responses induced at 2-6 weeks correlated with live viral neutralization at 6-months post-second dose, especially in hybrid immune individuals. Participants with pre-existing cross-reactive T-cell immunity to SARS-CoV-2 exhibited greater spike-specific T-cell responses, reduced anti-RBD IgA antibody levels, and a trending increase in neutralization at 2-6 weeks post-second dose. Non-spike-specific T-cells predominantly targeted SARS-CoV-2 non-structural protein at 6-months post-second dose in cross-reactive participants. mRNA vaccination was lastly shown to induce off-target T-cell responses against unrelated antigens. In summary, vaccine-induced spike-specific T-cell immunity appeared to influence serological neutralizing capacity, with only a modest effect induced by pre-existing cross-reactivity. IMPORTANCEOur findings provide important insights on the potential contributions of mRNA vaccine-induced spike-specific T-cell responses to the durability of neutralizing antibody levels in both uninfected and hybrid immune recipients. Our study additionally sheds light on the precise impacts of pre-existing cross-reactive T-cell immunity to SARS-CoV-2 on the magnitude and kinetics of cellular and humoral responses to vaccination. This study should ultimately inform the development of novel pan-coronavirus vaccines and vaccine regimens that can maximize the durability and breadth of protection against both current and future human coronaviruses of concern.

immunology↗

bioRxiv2023

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4+ T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV- participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were rescued after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV- participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral blips in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4+ T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

immunology↗

bioRxiv2022

Longitudinal Assessment of SARS-CoV-2 Specific T Cell Cytokine-Producing Responses for 1 Year Reveals Persistence of Multi-Cytokine Proliferative Responses, with Greater Immunity Associated with Disease Severity

Cellular-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 SARS-CoV-2-infected survivors over a one year post symptom onset (PSO) interval by ex vivo cytokine ELISpot assay. All subjects demonstrated SARS-CoV-2-specific IFN-{gamma}, IL-2, and Granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (Nucleocapsid, Membrane, Spike) except Envelope, with GzmB > IL-2 > IFN-{gamma}. Mathematical modeling predicted that: 1) cytokine responses peaked at 6 days for IFN-{gamma}, 36 days for IL-2, and 7 days for GzmB, 2) severe illness was associated with reduced IFN-{gamma} and GzmB, but increased IL-2 production rates, 3) males displayed greater production of IFN-{gamma}, whereas females produced more GzmB. Ex vivo responses declined over time with persistence of IL-2 in 86% and of IFN-{gamma} and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modelled to be 139 days ([~]4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the Nucleocapsid and Membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent. ImportanceOur findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control, shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and indicate robust persistence of T cell memory at least one year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.

immunology↗