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Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children

2022; American Society for Microbiology; Volume: 13; Issue: 6 Linguagem: Inglês

10.1128/mbio.01311-22

2161-2129

Jorge A. Soto, Felipe Melo-González, Cristián Gutiérrez-Vera, Bárbara M. Schultz, Roslye V. Berríos-Rojas, Daniela Rivera-Pérez, Alejandro Piña-Iturbe, Guillermo Hoppe-Elsholz, Luisa F. Duarte, Yaneisi Vázquez, Daniela Moreno-Tapia, Mariana Ríos, Pablo A Palacios, Richard García-Betancourt, Álvaro Santibáñez, Gaspar A. Pacheco, Constanza Méndez, Catalina A. Andrade, Pedro H. Silva, Benjamín Diethelm‐Varela, Patricio Astudillo, Mario Calvo, Antonio Cárdenas, Marcela González, Macarena Goldsack, Valentina Gutiérrez, Marcela Potı́n, Andrea Schilling, Lorena Tapia, Loreto Twele, Rodolfo Villena, Alba Grifoni, Alessandro Sette, Daniela Weiskopf, Rodrigo Fasce, Jorge Onrubia Fernández, Judith Mora, Eugenio Ramı́rez, Aracelly Gaete-Argel, Mónica L. Acevedo, Fernando Valiente‐Echeverría, Ricardo Soto‐Rifo, Angello Retamal‐Díaz, Nathalia Muñoz-Jofré, Xing Meng, Qianqian Xin, Eduardo Alarcón‐Bustamante, José Vicente González-Aramúndiz, Nicole Le Corre, María Javiera Álvarez-Figueroa, Pablo A. González, Katia Abarca, Cecilia Perret, Leandro J. Carreño, Susan M. Bueno, Alexis M. Kalergis, Patricio Astudillo, Epifanía Hernández Jara, Héctor Morán Fernández, Javiera Arenas Urra, Stephani Ascui Baeza, María Olivia Cabrera, José Romero Muñoz, Gonzalo Alarcón Andrade, Rocío Rodríguez Espósito, Anwar Gutiérrez Silva, Fernanda Pérez Gutiérrez, Alma Muñoz, Marcela Potin Santander, S.Mezquita Lopez, Tania Weil, Macarena Goldsack, Deidyland Arenas, Andrea Araya, Javiera Moore, Lorena Pilicita, Vania Valenzuela, Catalina Campos, Mauricio Soto, Andrea Schilling, Alberto Trautmann, Ana Fritis, Daniela Pavez, Javiera Arancibia, Lilian Rubio, Paula Viviani, Vinka Basic, Cassandra Cárcamo, Mario Calvo Gil, M. Wenzel, Nicole Carey, Roberto Aretxaga Burgos, Loreto Twele, Daniel Beltrán, Silvana Grandón, Carlos Tovar, Marcela González, Daniela Fuentes, Teresa Ramírez, Mariela Corrales, Nataly Martínez López, Valentina Gutiérrez, Felipe Reyes, Armando Lavayen, Melissa L. González, Monserrat Gutiérrez, Noris Rengifo, Carla Ortega, Florencia Saver, Lorena Tapia, Mirta Acuña, J. Carrillo de Albornoz, Tania Cariqueo, Alejandro Velásquez, Yennybeth Leiva Chamorro, Rodolfo Villena, Paola Flores, Francisca Bartsch, Belén Sepúlveda, Daniela Garmendia, Lorena González, Antonio Cárdenas, Angello Retamal, Carmen Ludeña, Carolina Hermosilla, Gustavo Keilhold, Francisco Cammarata‐Scalisi, Jessica Capón Álvarez, Jessica Romero, Pía Villarroel, Francisca Muñoz, Jorge Maya, Andrés Canales, Margarita K. Lay, Christian Muñoz, Roylester Araya,

Viral gastroenteritis research and epidemiology

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.