Directed attenuation to enhance vaccine immunity
| Autor: | Rustom Antia, Hasan Ahmed, James J. Bull |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
animal diseases Adaptive Immunity Mice Medical Conditions Medicine and Health Sciences Biology (General) Immune Response Innate Immune System Vaccines Attenuated vaccine Ecology Viral Vaccine Vaccination Infectious Disease Immunology Acquired immune system Infectious Diseases Computational Theory and Mathematics Virus Diseases Modeling and Simulation Viral growth Engineering and Technology Genetic Engineering Research Article Biotechnology Attenuated Vaccines Infectious Disease Control QH301-705.5 Immunology 030106 microbiology Bioengineering chemical and pharmacologic phenomena Biology Vaccines Attenuated Microbiology Virus 03 medical and health sciences Cellular and Molecular Neuroscience Th2 Cells Immune system Immunity Virology Genetics Animals Humans Molecular Biology Ecology Evolution Behavior and Systematics Immune Evasion Innate immune system Biology and Life Sciences Viral Vaccines Th1 Cells biochemical phenomena metabolism and nutrition Acquired Immune System Immunity Innate 030104 developmental biology Immune System bacteria Clinical Immunology Clinical Medicine |
| Zdroj: | PLoS Computational Biology, Vol 17, Iss 2, p e1008602 (2021) PLoS Computational Biology |
| ISSN: | 1553-7358 |
| Popis: | Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic engineering. However, even current methods operate on the principle of genetic harm, reducing the virus’s ability to grow. Reduced viral growth has the undesired side-effect of reducing the host immune response below that of infection with wild-type. Might some methods of attenuation instead lead to an increased immune response? We use mathematical models of the dynamics of virus with innate and adaptive immunity to explore the tradeoff between attenuation of virus pathology and immunity. We find that modification of some virus immune-evasion pathways can indeed reduce pathology yet enhance immunity. Thus, attenuated vaccines can, in principle, be directed to be safe yet create better immunity than is elicited by the wild-type virus. Author summary Live attenuated virus vaccines are among the most effective interventions to combat viral infections. Historically, the mechanism of attenuation has involved genetically reducing the viral growth rate, often achieved by adapting the virus to grow in a novel condition. More recent attenuation methods use genetic engineering but also are thought to impair viral growth rate. These classical attenuations typically result in a tradeoff whereby attenuation depresses the within-host viral load and pathology (which is beneficial to vaccine design), but reduces immunity (which is not beneficial). We use models to explore ways of directing the attenuation of a virus to avoid this tradeoff. We show that directed attenuation by interfering with (some) viral immune-evasion pathways can yield a mild infection but elicit higher levels of immunity than of the wild-type virus. |
| Databáze: | OpenAIRE |
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