Affiliation:
1. Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Kunming 650118, China
Abstract
Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5′ untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.
Funder
Major Science and Technology Special Project of Yunnan Province
Science and Technology Project of Yunnan Province—general program
CAMS Innovation Fund for Medical Sciences
Yunnan Province Innovative Vaccine Technology and Industrial Transformation Platform
Reference49 articles.
1. Rotavirus: Genetics, pathogenesis and vaccine advances;Sadiq;Rev. Med. Virol.,2018
2. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: A systematic review and meta-analysis;Tate;Lancet Infect. Dis.,2012
3. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015;Wang;Lancet,2016
4. Update on Rotarix: An oral human rotavirus vaccine;Linhares;Expert Rev. Vaccines,2009
5. RotaTeq: A three-dose oral pentavalent reassortant rotavirus vaccine;Chandran;Expert Rev. Vaccines,2009