Abstract

Respiratory syncytial virus (RSV) infection is the primary cause of respiratory infection in young children, causing >120,000 hospitalizations in the US annually. RSV vaccine development has been hampered by the history of a failed vaccine trial in the early 1960s in which vaccinated children were not protected against subsequent natural infection but rather experienced more severe disease. Subsequent experiments in animal models and human subjects suggest the occurrence of severe RSV disease correlates with the induction of virus-specific Th2 CD4 T cells and eosinophil recruitment and degranulation. The G glycoprotein of RSV and killed virus vaccines containing adjuvants such as alum induce these types of immune responses associated with the vaccine-enhanced disease syndrome. Dendritic cells are important for processing antigen and initiating immune responses. Understanding their interaction with RSV may reveal the reasons for relatively short-lived immunity induced by natural RSV infection. CD4 T cells can influence and regulate the function of other immune effectors including CD8 T cells. In addition to the potential role of Th2 CD4 T cells in RSV pathogenesis as mentioned above, T regulatory cells have properties that suggest they may be important in RSV immunity and pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005029-12
Application #
8745620
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$613,074
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Killikelly, April M; Kanekiyo, Masaru; Graham, Barney S (2016) Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci Rep 6:34108
Liu, Jie; Haddad, Elias K; Marceau, Joshua et al. (2016) A Numerically Subdominant CD8 T Cell Response to Matrix Protein of Respiratory Syncytial Virus Controls Infection with Limited Immunopathology. PLoS Pathog 12:e1005486
Kines, Rhonda C; Zarnitsyn, Vladimir; Johnson, Teresa R et al. (2015) Vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles. PLoS One 10:e0120797
Kiss, Gabriella; Holl, Jens M; Williams, Grant M et al. (2014) Structural analysis of respiratory syncytial virus reveals the position of M2-1 between the matrix protein and the ribonucleoprotein complex. J Virol 88:7602-17
Liu, Jie; Cao, Shirley; Peppers, Gretchen et al. (2014) Clonotype-specific avidity influences the dynamics and hierarchy of virus-specific regulatory and effector CD4(+) T-cell responses. Eur J Immunol 44:1058-68
Graham, Barney S (2013) Advances in antiviral vaccine development. Immunol Rev 255:230-42
Hillyer, Philippa; Raviv, Nataly; Gold, Doria M et al. (2013) Subtypes of type I IFN differentially enhance cytokine expression by suboptimally stimulated CD4(+) T cells. Eur J Immunol 43:3197-208
Collins, Peter L; Fearns, Rachel; Graham, Barney S (2013) Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease. Curr Top Microbiol Immunol 372:3-38
Johnson, Teresa R; Johnson, Christina N; Corbett, Kizzmekia S et al. (2011) Primary human mDC1, mDC2, and pDC dendritic cells are differentially infected and activated by respiratory syncytial virus. PLoS One 6:e16458
Liu, Jie; Ruckwardt, Tracy J; Chen, Man et al. (2010) Epitope-Specific Regulatory CD4 T Cells Reduce Virus-Induced Illness while Preserving CD8 T-Cell Effector Function at the Site of Infection. J Virol 84:10501-9

Showing the most recent 10 out of 12 publications