INNATE AND ADAPTIVE IMMUNE RESPONSES TO MEASLES AND THEIR ASSOCIATION WITH VIRAL CONTROL AND CLEARANCE

Measles;virus persistence;adaptive immunity;innate immunity;Th1;Th17;Tfh;Interferon;Immunology

Nelson, Ashley NMoss, William ;

Johns Hopkins University

关键词: Measles;    virus persistence;    adaptive immunity;    innate immunity;    Th1;    Th17;    Tfh;    Interferon;    Immunology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60208/NELSON-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Measles remains one of the most important causes of morbidity and mortality among children worldwide, despite the availability of a safe and effective vaccine. Measles virus, the etiologic agent of measles, is a member of the Paramyxoviridae family and has a negative-sense single-stranded RNA genome. The host immune response to measles is essential for viral clearance, recovery, and the establishment of long-term immunity. Paradoxically, measles is also associated with a transient state of immune suppression. In order to better understand the complexities of this disease we utilized the highly relevant rhesus macaque model.Use of the rhesus macaque model allowed us to study viral clearance, investigate the innate immune response, and characterize the dynamics of the adaptive immune response during a primary, wild-type measles virus infection. We show that viral RNA persists in multiple tissues and immune cells months after infectious virus is cleared. Additionally, we present a case that confirms that T cells play a vital role in viral clearance even in the absence of a neutralizing antibody response.The innate response to measles is particularly difficult to study in humans because the clinical diagnosis relies on the presence of a rash, which is a hallmark for the onset of the adaptive immune response. Using our rhesus macaque model, we were able to show that innate immunity to measles does not involve type I IFN production, indicating that activation of the adaptive immune response relies on other innate immune factors. We were further able to characterize the dynamics of the adaptive immune response to measles. Our work shows that the humoral immune response to measles virus involves the rapid production of virus-specific antibodies however, maturation of these responses are slow. We also demonstrate that virus-specific T cell responses are much more prolonged than previously recognized. This work provides new insight to our understanding of measles-induced immune suppression, the development of long-lived immunity, and occasional CNS complications due to viral persistence. Lastly, we analyzed the cellular immune response to a third dose of MMR and showed minimal boosting in immunity.