Development of a Lipopolysaccharide-Targeted Peptide Mimic Vaccine against Q Fever

Coxiella burnetii is a Gram-negative bacterium that causes acute and chronic Q fever in humans. Creation of a safe and effective new generation vaccine to prevent Q fever remains an important public health goal. Previous studies suggested that Ab-mediated immunity to C. burnetii phase I LPS (PI-LPS) is protective. To identify the potential peptides that can mimic the protective epitopes on PI-LPS, a PI-LPS-specific mAb 1E4 was generated, characterized, and used to screen a phage display library. Interestingly, our results indicate that 1E4 was able to inhibit C. burnetii infection in vivo, suggesting that 1E4 is a protective mAb. After three rounds of biopanning by 1E4 from the phage display library, a mimetic peptide, m1E41920, was identified, chemically synthesized, and conjugated to keyhole limpet hemocyanin (KLH) for examining its immunogenicity. The results indicate that the synthetic peptide m1E41920 was able to inhibit the binding of 1E4 to PI Ag, suggesting m1E41920 shares the same binding site of 1E4 with the epitopes of PI Ag. In addition, m1E41920-KLH elicited a specific IgG response to PI Ag, and immune sera from m1E41920-KLH-immunized mice was able to inhibit C. burnetii infection in vivo, suggesting that m1E41920 may specifically mimic the protective epitope of PI-LPS. Furthermore, m1E41920-KLH was able to confer significant protection against C. burnetii challenge. Thus, m1E41920-KLH is a protective Ag and may be useful for developing a safe and effective vaccine against Q fever. This study demonstrates the feasibility of developing a peptide mimic vaccine against Q fever.