RESUMO
Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.
RESUMO
Nesta investigação, as técnicas melhoradas por máquina foram aplicadas para trazer insights científicos para identificar um conjunto mínimo de biomarcadores relacionados à memória fenotípica / funcional para o acompanhamento pós-vacinação da vacinação contra a febre amarela (FA). Para este propósito, o estado de memória das células T circulantes (Naïve / efetor-precoce / Memória-Central / Memória Efetiva) e células B (Naïve / memória não clássica / memória clássica) juntamente com o perfil de citocinas (IFN / TNF / IL-5 / IL-10) foram monitorizados antes do NV (dia 0) e em pontos de tempo distintos após a vacinação primária com 17DD-YF - VP (dia30-45); PV (ano1-9) e PV (ano10-11). Um conjunto de biomarcadores (eEfCD4; EMCD4; CMCD19; EMCD8; IFNCD4; IL-5CD8; TNFCD4; IFNCD8; TNFCD8; IL-5CD19; IL-5CD4) foi observado em PV (dia30-45), mas não em NV (dia0) , com a maioria deles ainda observada em VP (ano1-9). Deficiências de biomarcadores fenotípicos / funcionais foram observadas em NV (dia 0), enquanto a falta total de atributos relacionados à memória foi observada na PV (ano10-11), independentemente da idade na vacinação primária. Análise de diagrama de Venn pré-selecionada 10 atributos (eEfCD4, EMCD4, CMCD19, EMCD8, IFNCD4, IL-5CD8, TNFCD4, IFNCD8, TNFCD8 e IL-5CD4), dos quais a média geral apresentou moderada precisão para discriminar PV (dia30-45) e PV (year1-9) de NV (day0) e PV (year10-11). Abordagens multi-parâmetro e algoritmos de árvore de decisão definiram os atributos EMCD8 e IL-5CD4 como os dois principais preditores com desempenho moderado. Juntamente com os títulos PRNT, os dois principais biomarcadores levaram a um status de memória resultante observado em 80% e 51% dos voluntários em PV (dia30-45) e PV (ano1-9), contrastando com 0% e 29% encontrados em NV ( day0) e PV (year10-11), respectivamente. A deficiência de atributos relacionados à memória observada na PV (year10-11) ressalta a diminuição conspícua dependente do tempo da memória resultante após a vacinação primária com 17DD-YF, que pode ser útil para monitorar potenciais correlatos de proteção em áreas sob risco de transmissão da FA.