Citation: Gil-Manso, S.; Carbonell, D.; Pérez-Fernández, V.A.; López-Esteban, R.; Alonso, R.; Muñoz, P.; Ochando, J.; Sánchez-Arcilla, I.; Bellón, J.M.; Correa-Rocha, R.; et al. Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines. Biomedicines 2022, 10, 1676. https://doi.org/10.3390/ biomedicines10071676 Academic Editor: Cinzia Giagulli Received: 10 June 2022 Accepted: 9 July 2022 Published: 12 July 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). biomedicines Article Cellular and Humoral Responses Follow-up for 8 Months after Vaccination with mRNA-Based Anti-SARS-CoV-2 Vaccines Sergio Gil-Manso 1 , Diego Carbonell 1,2 , Verónica Astrid Pérez-Fernández 1 , RocíoLópez-Esteban 3 , Roberto Alonso 4,5 , Patricia Muñoz 4,5 , Jordi Ochando 6,7 , Ignacio Sánchez-Arcilla 8 , Jose M Bellón 9 , Rafael Correa-Rocha 3 and Marjorie Pion 1, * 1 Advanced Immunoregulation Group, Gregorio Marañón Health Research Institute (IiSGM), Gregorio Marañón University General Hospital, 28009 Madrid, Spain; sergio.gil@iisgm.com (S.G.-M.); diegocarbonell3@gmail.com (D.C.); veronica.perez@iisgm.com (V.A.P.-F.) 2 Department of Hematology, Gregorio Marañón Health Research Institute (IiSGM), Gregorio Marañón University General Hospital, 28009 Madrid, Spain 3 Laboratory of Immune-Regulation, Gregorio Marañón Health Research Institute (IiSGM), Gregorio Marañón University General Hospital, 28009 Madrid, Spain; rocio.lopez@iisgm.com (R.L.-E.); rafael.correa@iisgm.com (R.C.-R.) 4 Department of Clinical Microbiology and Infectious Diseases, Gregorio Marañón University General Hospital, 28009 Madrid, Spain; roberto.alonso@salud.madrid.org (R.A.); pmunoz@hggm.es (P.M.) 5 School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain 6 Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; jochando@isciii.es 7 National Centre of Microbiology, Carlos III Health Institute, 28222 Madrid, Spain 8 Department of Occupational Risk Prevention, Gregorio Marañón University General Hospital, 28009 Madrid, Spain; ignacio.sanchezarcilla@salud.madrid.org 9 Department of Biostatistics, Gregorio Marañón Health Research Institute (IiSGM), Gregorio Marañón University General Hospital, 28009 Madrid, Spain; josemaria.bellon@salud.madrid.org * Correspondence: marjorie.pion@iisgm.com; Tel.: +34-664-43-44-02 Abstract: Vaccination against SARS-CoV-2 has become the main method of reducing mortality and severity of COVID-19. This work aims to study the evolution of the cellular and humoral responses conferred by two mRNA vaccines after two doses against SARS-CoV-2. On days 30 and 240 after the second dose of both vaccines, the anti-S antibodies in plasma were evaluated from 82 volunteers vaccinated with BNT162b2 and 68 vaccinated with mRNA-1273. Peripheral blood was stimulated with peptides encompassing the entire SARS-CoV-2 Spike sequence. IgG Anti-S antibodies (humoral) were quantified on plasma, and inflammatory cytokines (cellular) were measured after stimulation. We observed a higher response (both humoral and cellular) with the mRNA-1273 vaccine. Stratifying by age and gender, differences between vaccines were observed, especially in women under 48 and men over 48 years old. Therefore, this work could help to set up a vaccination strategy that could be applied to confer maximum immunity. Keywords: COVID-19; mRNA-vaccines; humoral responses; cellular responses; SARS-CoV-2 1. Introduction Since the apparition of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019 [1], several vaccine candidates have been developed, highlighting a novel type of vaccine based on mRNA. These mRNA-based vaccines have proven to be a great platform for designing specific vaccines against emerging infectious diseases because they present a versatile and rapid capacity to be designed against a specific antigen [2]. This novel approach was developed years ago [3,4], but the first mRNA vaccines commercially developed were those to confer immunity against SARS-CoV-2. The first two novel vaccines were the BNT162b2 [5] and mRNA-1273 [6], designed to confer protection against the spike protein from the initial SARS-CoV-2 strain (GenBank MN908947.3). This protein is responsible Biomedicines 2022, 10, 1676. https://doi.org/10.3390/biomedicines10071676 https://www.mdpi.com/journal/biomedicines