Avaliação da resposta específica de anticorpos de subclasses de IgG em indivíduos vacinados para COVID-19

Abstract

Introduction: COVID-19, a viral disease caused by SARS-CoV-2 infection, is characterized by its potential to cause severe cases of respiratory failure, leading to a pandemic with nearly 7million deaths and more than 700 million confirmed cases, which spurred the rapid development of vaccines. COVID-19 vaccination has altered the natural history of the disease, reducing deaths, severe cases, and SARS-CoV-2 infection. The importance of vaccines lies in their protective effect, achieved by stimulating the cellular and humoral immune responses induced by vaccination, which generate neutralizing and effector antibodies, cytokines, and memory T and B cells, thereby contributing to a better immune response in the individual. Consequently, several vaccines have been developed using different platforms. These include the ChAdOx1 nCoV-19 viral vector vaccine; the CoronaVac inactivated virus vaccine; and the BNT162b2 messenger RNA (mRNA) vaccine. Previous studies have demonstrated post-vaccination antibody responses against the spike protein and/or the RBD, including IgG (Immunoglobulin G), IgM (Immunoglobulin M), and IgA (Immunoglobulin A). However, few studies have examined the response of the IgG subclasses involved in the post-vaccination humoral response. The evaluation of the IgG1, IgG2, IgG3, and IgG4 subclasses allows for inferences about the functions of these antibodies, such as neutralization, complement fixation, and antibody-dependent cell-mediated cytotoxicity (ADCC). Objectives: To compare serum levels of IgG subclasses induced by the ChAdOx1 nCoV-19, CoronaVac, and BNT162b2 vaccines at different time points following vaccination. Methods: Whole blood samples from vaccinated individuals were collected from two cohorts at different time points: prior to the first dose, and after the second dose and booster dose. The first cohort comprised 74 vaccinated individuals, while the second cohort comprised 25 vaccinated individuals. Serological assays for IgG1, IgG3, and IgG4, following standardization tests, were performed using the enzyme-linked immunosorbent assay (ELISA) method for the Receptor-Binding Domain (RBD) protein. The results were expressed using the S/CO (Signal/Cutoff) index, calculated as the ratio of the mean optical density (OD) of the sample (duplicate) to the cutoff (mean value of the negative controls ± 2 times the standard deviation of the negative controls). Indices equal to or greater than 1.2 were used to represent the frequencies. Based on these results, nonparametric tests were performed using the Prisma software, version 9.0. Results: The study evaluated anti-RBD IgG1, IgG3, and IgG4 levels in relation to different vaccine types and doses at distinct collection time points. An induction of IgG1 and IgG3 levels was observed following vaccination with the primary doses of BNT162b2, ChAdOx1 nCoV-19, and CoronaVac, and following the booster dose of BNT162b2. The main subclass induced by vaccination with all vaccines was IgG1, with no difference observed between IgG3 and IgG4 levels. Subclass levels were also evaluated for the influence of factors such as sex, age, presence of comorbidities, overweight/obesity, and prior SARS-CoV-2 infection, revealing higher levels of IgG1 in women and individuals with comorbidities following the booster dose, regardless of vaccine type. Conclusion(s): IgG subclass responses are induced by vaccination in different ways depending on the dose and type of vaccine, with IgG1 proving to be the most prevalent subclass in the vaccine-induced response. Relevance and Impact: The study highlights the importance of understanding how IgG subclasses are induced and their dynamics, thereby enhancing our knowledge of the immune response to vaccination with different types of vaccines.