Unveiling Humoral and Cellular Immune Responses to SARS-CoV-2 in Head and Neck Cancer: A Comparative Study of Vaccination and Natural Infection in Romania

Marutescu, L.; Enea, A.; Antoniadis, N.-M.; Neculae, M.; Costea, D. A.; Popa, M.; Dragu, E.; Codrici, E.; Ristoiu, V.; Galateanu, B.; Hudita, A.; Pircalabioru, G. G.; Filali-Mouhim, A.; Lazar, V.; Chifiriuc, C.; Grigore, R.; Ancuta, P.

doi:10.1101/2024.10.27.620493

bioRxiv · 10.1101/2024.10.27.620493

Unveiling Humoral and Cellular Immune Responses to SARS-CoV-2 in Head and Neck Cancer: A Comparative Study of Vaccination and Natural Infection in Romania

Marutescu, L.·Enea, A.·Antoniadis, N.-M.·Neculae, M.·Costea, D. A.·Popa, M.·Dragu, E.·Codrici, E.·Ristoiu, V.·Galateanu, B.·Hudita, A.·Pircalabioru, G. G.·Filali-Mouhim, A.·Lazar, V.·Chifiriuc, C.·Grigore, R.·Ancuta, P.

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Abstract

BackgroundTo fill the knowledge gap regarding the antiviral immunity in oncologic patients, we performed a comparative study on natural/vaccine-induced SARS-CoV-2 immunity in head and neck cancer (HNC) in Romania. MethodsBlood was collected from HNC (n=49) and controls (n=14), stratified as vaccinated (RNA/adenovirus-based vaccines), convalescent, and hybrid immunity. Plasma IgG/IgA antibodies (Abs) against Spike (S1/S2), receptor binding domain (RBD), and nucleocapsid (NC), and cytokines were quantified using the MILLIPLEX(R) technology. The frequency/phenotype/isotype of RBD-specific B-cells were studied by flow cytometry using tetramers (Tet++). Cell proliferation in response to Spike/NC peptides was monitored by carboxyfluorescein succinimidyl ester (CFSE) assay. A longitudinal follow-up was performed on n=25 HNC. FindingsLevels of S1/S2/RBD-specific IgG/IgA Abs were similarly high in HNC and controls, but significantly increased in convalescent/hybrid versus vaccinated HNC. NC-specific IgG/IgA Abs were only detected in convalescent/hybrid immunity groups. The frequency of Tet++ B-cells in HNC was similar to controls, irrespective of the immunization status, and correlated positively with RBD IgG/IgA Abs and negatively with the time since immunization (TSI). Compared to total B-cells, Tet++ were enriched in CD27+ memory phenotype and IgG/IgA isotype. A linear regression model identified Spike S2 IgG and NC IgA Abs as strong positive predictors of Tet++ frequencies, while IL-6 was a marginally significant negative predictor. Tet++ frequency remained stable at median TSI of 341 versus 117 days, despite a decline in memory phenotype. InterpretationHNC participants mount efficient and durable SARS-CoV-2 humoral immunity, with RBD-specific IgG/IgA Abs and Tet++ B-cells representing the major immunization outcomes.

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Marutescu, L., Enea, A., Antoniadis, N.-M., Neculae, M., Costea, D. A., Popa, M., Dragu, E., Codrici, E., Ristoiu, V., Galateanu, B., Hudita, A., Pircalabioru, G. G., Filali-Mouhim, A., Lazar, V., Chifiriuc, C., Grigore, R., Ancuta, P.. 2024-10-29. Unveiling Humoral and Cellular Immune Responses to SARS-CoV-2 in Head and Neck Cancer: A Comparative Study of Vaccination and Natural Infection in Romania. https://doi.org/10.1101/2024.10.27.620493

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