Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses.
Takahiro KawagishiLiliana Sánchez-TacubaNingguo FengVeronica P CostantiniMing TanXi JiangKim Y GreenJan VinjéSiyuan DingHarry B GreenbergPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo . This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens.
Keyphrases
- mycobacterium tuberculosis
- endothelial cells
- high fat diet induced
- protein protein
- induced pluripotent stem cells
- cell free
- amino acid
- pluripotent stem cells
- high glucose
- binding protein
- wild type
- drug induced
- induced apoptosis
- dendritic cells
- gram negative
- multidrug resistant
- antimicrobial resistance
- genome wide
- dna methylation
- oxidative stress
- small molecule
- copy number
- adipose tissue
- cell death
- human health
- diabetic rats
- endoplasmic reticulum stress