Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute and chronic Q fever in humans. It is an understudied category B select agent and can be transmitted via aerosol. The existing formalin-inactivated phase I whole-cell vaccine (PIV) induces serious side effects in previously sensitized individuals and no vaccine is commercially available for prevention of human Q fever in the US. Therefore, creation of a safe and effective vaccine to prevent Q fever remains an important public health and national biosecurity goal. Our long-term goal is to develop novel approaches for safe and effective immunoprophylaxis of acute and chronic Q fever. Interestingly, our preliminary studies demonstrated that a peptide mimic of a C. burnetii phase I lipopolysaccharide (PI-LPS) epitope (m1E41920) conjugated to keyhole limpet haemocyanin (m1E41920-KLH) conferred protection against C. burnetii infection in both mouse and guinea pig models. These findings support the utility of m1E41920 as a vaccine candidate to prevent human Q fever. Thus, the objective of this revised R01 application is to define and optimize a PI-LPS-mimetic peptide and recombinant protein combination vaccine that confers the same level of protection as the PIV. To achieve this objective, we propose three specific aims to test the central hypothesis that the combination of m1E41920 with additional protective peptide mimic of PI-LPS and recombinant C. burnetii protein antigens will confer the same level of protection as the PIV.
Aim 1 will use a C. burnetii aerosol infection mouse model to define and optimize a PI- LPS-mimetic peptide and recombinant protein combination vaccine that will confer the same level of protection as the PIV.
Aim 2 will determine if the protective epitopes of PIV recognized by the mouse model will confer adequate protection in a guinea pig aerosol infection model.
Aim 3 will use a humanized mouse model to determine if the protective epitopes of PIV recognized by rodents will confer protection in humans. Upon the completion of the proposed research, we expect to define the first multivalent vaccine for Q fever targeting novel neutralization-sensitive epitopes of both PI-LPS and PI protein. This will have significant positive effects on human health, because it will provide the basic information required to ultimately develop a safe, effective and tractable vaccine against Q fever.

Public Health Relevance

Development of a safe and effective vaccine for prevention of human Q fever remains an important goal for public health and national biosecurity. To achieve this goal, this application aims to define the first multivalent vaccine for Q fever targeting both C. burnetii phase I lipopolysaccharide and protein.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI134681-03
Application #
10005679
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Zou, Lanling
Project Start
2018-08-13
Project End
2022-07-31
Budget Start
2019-11-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
800189185
City
San Antonio
State
TX
Country
United States
Zip Code
78249