mBio (Dec 2022)

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

  • Jorge A. Soto,
  • Felipe Melo-González,
  • Cristián Gutierrez-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 Garcia-Betancourt,
  • Álvaro Santibañez,
  • Gaspar A. Pacheco,
  • Constanza Mendez,
  • Catalina A. Andrade,
  • Pedro H. Silva,
  • Benjamín Diethelm-Varela,
  • Patricio Astudillo,
  • Mario Calvo,
  • Antonio Cárdenas,
  • Marcela González,
  • Macarena Goldsack,
  • Valentina Gutiérrez,
  • Marcela Potin,
  • Andrea Schilling,
  • Lorena I. Tapia,
  • Loreto Twele,
  • Rodolfo Villena,
  • Alba Grifoni,
  • Alessandro Sette,
  • Daniela Weiskopf,
  • Rodrigo A. Fasce,
  • Jorge Fernández,
  • Judith Mora,
  • Eugenio Ramírez,
  • 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 V. González-Aramundiz,
  • Nicole Le Corre,
  • María Javiera Álvarez-Figueroa,
  • Pablo A. González,
  • Katia Abarca,
  • Cecilia Perret,
  • Leandro J. Carreño,
  • Susan M. Bueno,
  • Alexis M. Kalergis

DOI
https://doi.org/10.1128/mbio.01311-22
Journal volume & issue
Vol. 13, no. 6

Abstract

Read online

ABSTRACT 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.

Keywords