Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells
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...
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MDPI AG
2020-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/1/144 |
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| author | Yingying Li Ling Zhao Baokui Sui Zhaochen Luo Yachun Zhang Yong Wang |
| author_facet | Yingying Li Ling Zhao Baokui Sui Zhaochen Luo Yachun Zhang Yong Wang |
| author_sort | Yingying Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:57:02Z |
| format | Article |
| id | doaj.art-5a9943d73dcd4cbfa2638b080cffa4e8 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T13:57:02Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-5a9943d73dcd4cbfa2638b080cffa4e82022-12-22T04:20:18ZengMDPI AGVaccines2076-393X2020-03-018114410.3390/vaccines8010144vaccines8010144Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B CellsYingying Li0Ling Zhao1Baokui Sui2Zhaochen Luo3Yachun Zhang4Yong Wang5Department of Human Anatomy, College of Basic Medicine, Dali University, Dali 671000, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, ChinaDepartment of Human Anatomy, College of Basic Medicine, Dali University, Dali 671000, ChinaRabies, 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.https://www.mdpi.com/2076-393X/8/1/144rabies vaccineox40-ligandt follicular helper cellsgerminal center b cellsplasma cells |
| spellingShingle | Yingying Li Ling Zhao Baokui Sui Zhaochen Luo Yachun Zhang Yong Wang Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells Vaccines rabies vaccine ox40-ligand t follicular helper cells germinal center b cells plasma cells |
| title | Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells |
| title_full | Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells |
| title_fullStr | Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells |
| title_full_unstemmed | Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells |
| title_short | Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells |
| title_sort | recombinant rabies virus overexpressing ox40 ligand enhances humoral immune responses by increasing t follicular helper cells and germinal center b cells |
| topic | rabies vaccine ox40-ligand t follicular helper cells germinal center b cells plasma cells |
| url | https://www.mdpi.com/2076-393X/8/1/144 |
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