Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells.
Yingying LiLing ZhaoBaokui SuiZhaochen LuoYachun ZhangYong WangPublished in: Vaccines (2020)
Rabies, caused by the rabies virus (RABV), remains a serious threat to public health in most countries. Development of a single-dose and efficacious rabies vaccine is the most important method to restrict rabies virus transmission. Costimulatory factor OX40-ligand (OX40L) plays a crucial role in the T cell-dependent humoral immune responses through T-B cell interaction. In this work, a recombinant RABV overexpressing mouse OX40L (LBNSE-OX40L) was constructed, and its effects on immunogenicity were evaluated in a mouse model. LBNSE-OX40L-immunized mice generated a larger number of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs) than the parent virus LBNSE-immunized mice. Furthermore, LBNSE-OX40L induced significantly higher levels of virus-neutralizing antibodies (VNA) as early as seven days post immunization (dpi), which lasted for eight weeks, resulting in better protection for mice than LBNSE (a live-attenuated rabies vaccine strain). Taken together, our data in this study suggest that OX40L can be a novel and potential adjuvant to improve the induction of protective antibody responses post RABV immunization by triggering T cell-dependent humoral immune responses, and that LBNSE-OX40L can be developed as an efficacious and nonpathogenic vaccine for animals.
Keyphrases
- immune response
- induced apoptosis
- public health
- low density lipoprotein
- cell cycle arrest
- dendritic cells
- mouse model
- endoplasmic reticulum stress
- high fat diet induced
- toll like receptor
- signaling pathway
- cell death
- wastewater treatment
- risk assessment
- adipose tissue
- inflammatory response
- endothelial cells
- cell proliferation
- skeletal muscle
- disease virus
- high glucose
- drug induced