According to results from a placebo-controlled, phase 1/2 study published in Vaccine, a 4-antigen vaccine currently under development for prevention of invasive Staphylococcus aureus disease (SA4Ag) demonstrated rapid and robust functional immune responses that were durable through month 12.1 SA4Ag had an acceptable safety profile for the 3 dose levels that were tested, with no vaccine-related serious adverse events reported. Designed to counter multiple bacterial virulence factors, SA4Ag is intended to intercept S aureus at the early stages of invasive infection, before the development of biofilms or foci that may impede immune intervention.
Prior attempts to develop an S aureus vaccine were unsuccessful. “The thought is that having multiple antibodies will be more effective in blocking infection with this difficult infection,” lead investigator Robert W. Frenck Jr, MD, told Infectious Disease Advisor. “It is possible that previous vaccines were not successful due to being a single antigen.”
SA4Ag is a refinement of a preliminary 3-antigen vaccine against S aureus that had previously been shown to be safe and immunogenic. Antigens in that vaccine consisted of antiphagocytic capsular polysaccharides CP5-CRM197 and CP8-CRM197 and the adhesion molecule rmClfA. For the current study, rP305A, a novel manganese transporter protein, was added. Three different amounts of rP305A were tested in conjunction with fixed amounts of the other 3 antigens. Confirming previous studies, the immune responses to CP5-CRM197, CP8-CRM197, and rmClfA were brisk, had high titers by 2 weeks after vaccination, and persisted for at least a year after vaccination. rP305A also demonstrates a brisk response by 2 weeks after vaccination and persistence for a year after vaccination. In addition, increasing the dosage of rP305A was associated with an increase in antibody production.
“There are multiple potential clinical benefits for a vaccine against S aureus,” noted Dr Frenck. “[These include] prevention of skin/soft tissue infections in children, prevention of infections in people undergoing dialysis, and prevention of infection among patients undergoing procedures at higher risk for acquiring Staph infections such as spinal fusion and surgery requiring opening of the chest cavity. The exciting finding of the 4-antigen vaccine that we tested was the development of a rapid antibody response, which suggests vaccination is feasible to prevent infections associated with planned surgeries.”
The US Food and Drug Administration has granted SA4Ag a Fast Track designation, meaning it qualifies for priority review.2 The Fast Track process is designed to expedite the review of drugs that treat serious conditions and fill an unmet medical need. A phase 2b study to demonstrate SA4Ag efficacy in adults undergoing elective spinal fusion surgery is currently underway, with an expected completion date of November 2018.3
- Frenck RW, Buddy Creech C, Sheldon EA, et al. Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study. Vaccine. 2017;35(2):375-384. doi: 10.1016/j.vaccine.2016.11.010
- Giersing BK, Dastgheyb SS, Modjarrad K, Moorthy V. Status of vaccine research and development of vaccines for Staphylococcus aureus. Vaccine. 2016;34(26):2962-2966. doi:10.1016/j.vaccine.2016.03.110
- ClinicalTrials.gov. Safety and Efficacy of SA4Ag Vaccine in Adults Having Elective Open Posterior Spinal Fusion Procedures With Multilevel Instrumentation (STRIVE). NCT02388165. https://clinicaltrials.gov/ct2/show/NCT02388165. Accessed January 16, 2017.