T Cell Responses to BA.2.86 and JN.1 SARS-CoV-2 Variants in Elderly Subjects.

Publication date: Dec 23, 2024

New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA. 2.86 and JN. 1 variants, particularly in elderly individuals. We evaluated T cell and total IgG responses against the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 strain, as well as BA. 2.86 and JN. 1 omicron subvariants, in two groups of subjects. One group consisted of SARS-CoV-2-exposed elderly individuals who were fully vaccinated with the BNT162B2 mRNA vaccine, with a booster dose of the updated 2023-2024 COVID-19 vaccine (XBB. 1.5) at least 15 days after receiving a booster dose of the updated 2023-2024 COVID-19 vaccine. The second group consisted of healthcare workers who were unexposed to SARS-CoV-2 one month after the booster dose of the first-generation BNT162b2 mRNA vaccine. T cell activation-induced markers (AIM) and IFN-γ secretion were evaluated by flow cytometry and ELISpot assays, respectively. Elderly subjects showed reduced IgG levels against JN. 1 compared with the ancestral strain. BA. 2.86 stimulation resulted in lower IFN-γ levels in the elderly versus the COVID-19-nacEFve group. AIM analysis showed that among T cells, CD4+ were the most responsive, with a reduced proportion of JN. 1-reactive CD4+ T cells compared with the ancestral strain in the SARS-CoV-2-unexposed group. Despite receiving the updated booster, the elderly group showed reduced CD4+ T cell reactivity to BA. 2.86. The XBB. 1.5-containing vaccine induced lower CD4+ T cell responses against BA. 2.86 in the elderly. CD4+ T cells from BNT16b2-vaccinated, COVID-19-nacEFve subjects recognized ancestral and BA. 2.86 RBD strains while showing reduced responses to JN. 1. These results emphasize the need for tailored vaccine strategies for emerging variants, particularly in vulnerable populations.

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Concepts Keywords
Cd4 BA.2.86
Elderly COVID-19
Healthcare elderly
Mrna JN.1
SARS-CoV-2
vaccine

Semantics

Type Source Name
disease IDO cell
disease MESH COVID-19
disease MESH Infectious Diseases
drug DRUGBANK Coenzyme M
disease MESH infection
disease IDO host
disease IDO infectivity
disease IDO protein
disease IDO blood
drug DRUGBANK Trestolone
drug DRUGBANK Edetic Acid
disease MESH COPD
disease MESH chronic renal failure
disease MESH autoimmune diseases
disease MESH neoplasms
disease IDO history
disease IDO assay
drug DRUGBANK Alkaline Phosphatase
drug DRUGBANK Streptomycin
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK Immune Globulin Human
disease MESH cardiovascular diseases
disease MESH Heart failure
disease MESH Stroke
disease MESH Intestinal Obstruction
disease MESH pulmonary disease
pathway REACTOME Immune System
disease IDO production
disease MESH breakthrough infections

Original Article

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