An Immunodominant Epitope-Specific Monoclonal Antibody Cocktail Improves Survival in a Mouse Model ofStaphylococcus aureusBacteremia

Abstract

To date, no vaccine or monoclonal antibody (mAb) against S. aureus has been approved for use in humans. Our lab has developed a five-antigen S. aureus vaccine (rFSAV), which is now under efficacy evaluation in a phase II clinical trial. In the current study, using overlapping peptides and antiserum from rFSAV-immunized volunteers, we identified seven B-cell immunodominant epitopes on 4 antigens in rFSAV, including five novel epitopes (Hla48-65, IsdB402-419, IsdB432-449, SEB78-95 and MntC7-24). Ten immunodominant-epitope mAbs were generated against these epitopes, and all of them exhibited partial protection in a mouse sepsis model. Four robust mAb were used together as a mAb cocktail to prevent MRSA252 infection. The results showed that the mAb cocktail was efficient in combating S. aureus infection and that its protective efficacy correlated with a reduced bacterial burden, and decreased infection pathology, which demonstrates that the mAb cocktail is a promising S. aureus vaccine candidate.

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

“…BALB/c mice were immunized with HI plus different adjuvants on days 0, 14 and 21 and then challenged with a lethal dose of MRSA252 one week after the last immunization. As shown in Figure 1A, all mice in the PBS-immunized group died within 4 days after MRSA252 infection, consistent with our previous studies and indicating that the bacteremia model was successful (13). In contrast, mice immunized with HI and different adjuvants exhibited different protective efficacies.…”

“…These results suggested that adjuvants are capable of driving the immunodominant response toward the same antigen, resulting in differences in protective efficacy. Meanwhile, the immunodominant epitope Hla 42-59 identified in this study may share the same B cell epitope in Hla 48-65 , which was previously identified using serum from humans(13). The other six epitopes…”

“…Taking this into consideration, we identified 3 immunodominant epitopes on HI using serum from immunized individuals in a phase I clinical trial, which was performed to evaluate the safety and immunogenicity of rFSAV. Monoclonal antibodies recognizing these epitopes were also protective against S. aureus infection (13), further confirming the importance of immunodominant epitopes for inducing protective immunity.…”

Current and Future Landscape of the Antimicrobial Resistance of Nosocomial Infections in China

“…Antimicrobial peptides primarily act to suppress or kill pathogenic microorganisms by processes such as cell wall and membrane destruction, induction of changes in metabolic enzyme activity, and host immunological control (16). The current issue, in which the progress of antibiotic development cannot keep pace with the increase in resistance to new antibiotics, may be resolved by the development of immunotherapy (17). The most commonly explored bacterial vaccines are whole-bacteria-inactivated or attenuated vaccines, outer membrane vesicles, recombinant DNA, and capsular polysaccharide vaccines.…”

“…The most commonly explored bacterial vaccines are whole-bacteria-inactivated or attenuated vaccines, outer membrane vesicles, recombinant DNA, and capsular polysaccharide vaccines. The first recombinant S. aureus vaccine has been approved by China’s State Food and Drug Administration for phase III clinical research ( 18 ). Furthermore, the phage can self-replicate and, when used therapeutically, improve the effectiveness of antibiotics.…”