Impact of repeated vaccination on the effectiveness of seasonal influenza vaccines Summary Influenza viruses cause pandemic and seasonal outbreaks that lead to the loss of thousands to millions of human lives. Vaccination is the best option for preventing influenza outbreaks and minimizing their effects on health. In the United States, annual influenza vaccination has been recommended since 2010 for persons 6 months of age and older. However, vaccine performance varies significantly between influenza seasons, and reduced vaccine effectiveness has been observed. Studies have reported that persons vaccinated during two consecutive influenza seasons had lower vaccine effectiveness during the second season than persons who had not been vaccinated during the prior season. These findings have caused profound confusion among the public regarding the potential benefit of annual influenza vaccination. Thus, there is a critical need to address the effect of repeated vaccination?associated pre-existing immunity on influenza vaccine performance. The objective of this project is to characterize the effects of repeated influenza vaccination on the specificity and magnitude of cross-reactive antibodies and on the effectiveness of seasonal influenza vaccines.
Two specific aims are proposed: 1) determine the specificity, magnitude, and longitudinal patterns of humoral responses in humans with repeated seasonal vaccination, and 2) test the effect of repeated vaccination? associated pre-existing immunity on influenza vaccine performance in ferrets. By comparing antibodies in persons with and without repeated influenza vaccination, we expect to show whether and how pre-existing immunity achieved through repeated influenza vaccination affects the specificity and magnitude of the cross-reactivity for the resulting antibodies and, thus, vaccine effectiveness. From our studies in ferrets, we expect to show whether and how variations in repeated vaccination?associated pre- existing immunity affect influenza vaccine performance. This study will expand our understanding of molecular mechanisms that may influence how repeated vaccination affects influenza vaccine performance. Thus, this study will provide basic knowledge for evaluating the need for annual influenza vaccination and for optimizing influenza vaccine performance.

Public Health Relevance

The objective of this project is to characterize the effects of repeated influenza vaccination on the specificity of cross-reactive antibodies and on influenza vaccine performance. The study findings will enable optimization of influenza vaccine performance by expanding our understanding of molecular mechanisms involved in the effect of repeated influenza vaccination on vaccine performance and by providing basic knowledge to evaluate the need for annual influenza vaccination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI152521-01
Application #
9998504
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Lane, Mary Chelsea
Project Start
2020-03-03
Project End
2025-02-28
Budget Start
2020-03-03
Budget End
2021-02-28
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211