In 1967, the formalin-inactivated vaccine against respiratory syncytial virus (RSV) primed infants and children to develop an enhanced form of lower respiratory tract disease upon exposure to RSV in the community. Thirty-seven years later, the mechanism of illness of this enhanced disease remains unclear. Furthermore, why inactivated vaccines against this virus elicit non-protective antibody is not understood. No vaccine against RSV has been licensed since. We use a novel mouse model of enhanced disease to address these questions. We hypothesize that affinity maturation of RSV-specific B cells is required for development of a protective antibody response against RSV. We further hypothesize that immunization of RSV- naive mice with nonreplicating RSV vaccines activates B cells that do not undergo affinity maturation and therefore elicits a non-protective RSV-specific antibody response. This non-protective response results in immune complex formation and deposition in the lungs and enhanced disease. We propose the following Specific Aims: 1) Determine whether the method of RSV inactivation is important for vaccine-enhanced disease. 2) Determine the role of RSV F and G protective antigens in vaccine-enhanced disease. 3) Determine whether vaccine-enhanced disease is associated with the lack of affinity maturation of the B cell response to FIRSV, and therefore can be prevented by promoting affinity maturation of the B cell response to FIRSV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI054952-02
Application #
7024542
Study Section
Special Emphasis Panel (ZRG1-VMD (01))
Program Officer
Cho, David
Project Start
2005-03-15
Project End
2010-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
2
Fiscal Year
2006
Total Cost
$358,865
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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