Combining SARS‐CoV‐2 interferon‐gamma release assay with humoral response assessment to define immune memory profiles

• Published in: European journal of immunology 2024-07, Vol.54 (7), p.e2451035-n/a
• Main Authors: Mouton, William, Oriol, Guy, Compagnon, Christelle, Saade, Carla, Saker, Kahina, Franc, Priscille, Mokdad, Bouchra, Fleurie, Aurore, Lacoux, Xavier, Daniel, Soizic, Berthier, Franck, Barnel, Cécile, Pozzetto, Bruno, Fassier, Jean‐Baptiste, Dubois, Valérie, Djebali, Sophia, Dubois, Maxence, Walzer, Thierry, Marvel, Jacqueline, Brengel‐Pesce, Karen, Trouillet‐Assant, Sophie
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adult; Antibodies, Viral - blood; Antibodies, Viral - immunology; Cell-mediated immunity; COVID-19 - immunology; COVID-19 Vaccines - immunology; Female; Health Personnel; Humans; Humoral immunity; Immune memory profile; Immune response (humoral); Immunity, Humoral - immunology; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunologic Memory - immunology; Immunological memory; Infections; Interferon; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interferon-gamma Release Tests - methods; Interferon‐gamma release assay; Male; Medical personnel; Middle Aged; Prophylaxis; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocytes - immunology; Vaccination
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202451035

Objectives In the post‐SARS‐CoV‐2 pandemic era, “breakthrough infections” are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti‐Spike (S) immunoglobulin‐G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T‐cell response assessment to enhance the definition of immune memory profile. Methods SARS‐CoV‐2 interferon‐gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti‐receptor‐binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated. Results Close to 40% of our samples were exclusively IGRA‐positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long‐lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti‐receptor‐binding domain IgG and IGRA levels tended to reduce it. Conclusion The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level. Cell‐mediated immunity and humoral response appeared as essential in the protection against SARS‐CoV‐2 infection. We performed a whole‐blood Interferon‐gamma release assay alongside anti‐RBD‐IgG quantification in a population of immunocompetent healthcare workers followed longitudinally. We report that implementing T‐cell response monitoring offers additional insights to delineate a more comprehensive individual immune profile.