Enhancement of Immune Memory Responses to Respiratory Infection
Abstract
The proposed research is in direct response to the Fiscal Year 2014 Peer Reviewed Medical Research Program Topic Area "Respiratory Health." Influenza infection claims around half million lives around the world each year, while the World Health Organization estimates put the yearly cost of influenza epidemics to the US economy at over $100 billion. Despite advances in modern medicine, vaccines remain the most effective strategy to prevent influenza epidemics. Maintenance of long-term immunological memory against influenza virus is the basis for most currently available vaccines. However, the molecular mechanisms that govern persistence of vaccine-mediated immune memory responses have not been fully explored. We have recently found that a particular family involved in the protection of cells called autophagy genes are highly expressed in a special subset of white blood cells (a.k.a. B lymphocytes) and are responsible for the protection against influenza virus. In mice, autophagy 7 is required for the maintenance of protective B-lymphocytes (memory B cells) needed to fight against influenza infection. Mice with B cell-specific deficiency in autophagy 7 show accelerated memory B cell death after immunization with influenza, and they succumb to influenza infection due to failure to generate protective secondary antibody responses. Human influenza-specific memory B cells also have high levels of autophagy, but whether autophagy protects memory B cell survival in humans remains unknown. Further, chronic obstructive pulmonary disease (COPD) exacerbation due to influenza results in a large number of hospitalizations and increased mortality in smokers even if they routinely receive the vaccine. Whether ineffective influenza vaccination in COPD is in part due to failure to maintain influenza-specific memory B cells remains to be determined. The goals of this application are to determine the cellular and molecular mechanisms responsible for the maintenance of memory B cells against influenza and to explore novel means to boost autophagy in memory B cells and the production of neutralizing antibody in smokers with COPD that are vulnerable to influenza infection. Our findings will facilitate the development of improved vaccine strategies to protect against influenza infection in normal and in highly vulnerable populations such as smokers with COPD by promoting autophagy. The proposed study has direct relevance to the healthcare needs of military Service members, Veterans, and beneficiaries, who are at greater risk to be exposed to influenza and other respiratory infectious agents. Our work may also provide a mechanistic frame for other investigators who are studying vaccination against other respiratory viruses, bacteria, parasites, and cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610360
Entities
People
- Min Chen
Organizations
- Baylor College of Medicine
- United States Army