Yi Wang1*†, Xiaoxia Wang2†, Laurence Don Wai Luu3†, Shaojin Chen2, Fu Jin1, Shufang Wang4, Xiaolan Huang1, Licheng Wang2, Xiaocui Zhou2, Xi Chen2, Xiaodai Cui1, Jieqiong Li5*, Jun Tai6* and Xiong Zhu2*

• 1Experimental Research Center, Capital Institute of Pediatrics, Beijing, China
• 2Central & Clinical Laboratory of Sanya People’s Hospital, Sanya, China
• 3School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, NSW, Australia
• 4Nursing department of Sanya People’s Hospital, Sanya, China
• 5Department of Respiratory Disease, Beijing Pediatric Research Institute, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
• 6Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital Capital Institute of Pediatrics, Beijing, China

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results help us to understand the host response to vaccination of CoronaVac and highlight the utility of a systems biology approach in defining molecular correlates of protection to vaccination.

Full article: https://www.frontiersin.org/articles/10.3389/fimmu.2022.848961/full