| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Yi, Yinglei Li, Changgui Li, Xuguang Jaentschke, Bozena Wang, Junzhi Hashem, Anwar M. Pereboev, Alexander Tocchi, Monika Gravel, Caroline Rosu-Myles, Michael He, Runtao Fan, Xingliang Chen, Ze |
| Description |
Author Affiliation: Hashem AM ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada); Gravel C ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada); Chen Z ( Shanghai Institute of Biological Products, Shanghai 200231, China); Yi Y ( Shanghai Institute of Biological Products, Shanghai 200231, China); Tocchi M ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada); Jaentschke B ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada); Fan X ( National Institutes for the Control of Food and Drug, Beijing 10050, People's Republic of China); Li C ( National Institutes for the Control of Food and Drug, Beijing 10050, People's Republic of China); Rosu-Myles M ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada); Pereboev A ( Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294); He R ( National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada); Wang J ( National Institutes for the Control of Food and Drug, Beijing 10050, People's Republic of China); Li X ( Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario K1A 0K9, Canada) |
| Abstract |
CD40L, a key regulator of the immune system, was studied as both a targeting ligand and a molecular adjuvant in nucleoprotein (NP)-based host defense against influenza in mouse models with different genetic backgrounds. Adenoviral vectors secreting NP-CD40L fusion protein (denoted as rAd-SNP40L) afforded full protection of immunocompetent and immunocompromised mice (CD40L(-/-) and CD4(-/-)) against lethal influenza infection. Mechanistically, rAd-SNP40L preferentially induced early and persistent B cell germinal center formation, and accelerated Ig isotype-switching and Th1-skewed, NP-specific Ab response. Moreover, it drastically augmented primary and memory NP-specific CTL activity and polyfunctional CD8(+) T cells. The markedly enhanced nonneutralizing Abs and CTLs significantly reduced viral burdens in the lungs of mice upon lethal virus challenge. Data generated from CD40L(-/-) and CD4(-/-) mice revealed that the protection was indeed CD40L mediated but CD4(+) T cell independent, demonstrating the viability of the fusion Ags in protecting immunodeficient hosts. Notably, a single dose of rAd-SNP40L completely protected mice from lethal viral challenge 4 mo after immunization, representing the first report, to our knowledge, on NP in conjunction with a molecular adjuvant inducing a robust and long-lasting memory immune response against influenza. This platform is characterized by an increased in vivo load of CD40-targeted Ag upon the secretion of the fusion protein from adenovirus-infected cells and may represent a promising strategy to enhance the breadth, durability, and potency of Ag-specific immune responses. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Adaptive Immunity Immunology Cd40 Ligand Influenza A Virus Orthomyxoviridae Infections Genetics Adenoviridae Animals B-lymphocytes Metabolism Cd4-positive T-lymphocytes Deficiency Cd8-positive T-lymphocytes Genetic Vectors Hek293 Cells Immunization Physiology Madin Darby Canine Kidney Cells Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Nih 3t3 Cells Nucleoproteins Virology Recombinant Fusion Proteins Survival Analysis T-lymphocytes, Cytotoxic Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
