Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses  

作　　者：Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei 

机构地区：[1]Laboratory of Aging Research and Cancer Drug Target,State Key Laboratory of Biotherapy and Cancer Center,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China

出　　处：《Genes & Diseases》2024年第4期327-339,共13页基因与疾病（英文）

基　　金：funded by the National Science Foundation for Excellent Young Scholars of China(No.32122052);the National Natural Science Foundation Regional Innovation and Development of China(No.U19A2003).

摘　　要：The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient protection.Intranasal immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of SARS-CoV-2.In this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA vaccine.After intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 receptors.Furthermore,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and spleen.Collectively,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关 键 词：Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine 

分 类 号：R392-33[医药卫生—免疫学]