PHILADELPHIA – A single injection of the investigational 4-antigen SA4Ag vaccine was well tolerated and induced robust antibody responses against Staphylococcusaureus in healthy adults in a phase I/II study.
“The very quick development of antibodies suggest that the vaccine could be used pre-operatively [2-3 weeks] for elective surgeries that are at higher risk of Staph. infection, such as thoracotomy or insertion of rods for scoliosis or spinal fusion,” Dr. Robert W. Frenck Jr. said in an interview at Infectious Diseases Week 2014.
As to the durability of responses, antibody levels for all four antigens in the vaccine rose rapidly and then decayed slowly over the next 12 months, he said. “The results support the continued development of SA4Ag for the prevention of invasive S. aureus disease in at-risk adults, including those undergoing elective surgery.”
There is no licensed vaccine that prevents invasive S. aureus infection, although several multi-antigen vaccines are in development.
SA4Ag vaccine is a second-generation vaccine to Pfizer’s 3-antigen SA3AG candidate vaccine and was granted Fast Track designation by the U.S. Food and Drug Administration in February 2014, according to the manufacturer.
SA4Ag contains capsular polysaccharides serotypes 5 and 8 (CP5 and CP8) individually conjugated to CRM₁₉₇, a recombinant surface protein clumping factor A (rmClfA), with a recombinant manganese transporter protein C known as rP305A. Each component was selected based on the virulence of these antigens in S. aureus infections, Dr. Frenck Jr., professor of pediatrics and interim director of infectious diseases, at Cincinnati (Ohio) Children’s Hospital Medical Center, said.
The study stratified 456 healthy adults by age (18-49 years and 50-64 years) and then randomly assigned them to receive a single injection of placebo or one of three formulations of SA4Ag: fixed doses of 30 μg CP5-CRM₁₉₇, 30 μg CP8-CRM₁₉₇, and 60 μg rmClfA, and either a low- (20 μg), mid- (60 μg), or high- (200 μg) rP305A dose.
The participants average age was 45 years, 57% were female, 73% were white, and 87.5% completed the study through month 12.
Local reactions reported through day 14 were mild or moderate, and systemic events and other adverse events were comparable across all groups, Dr. Frenck Jr. said. No vaccine-related serious adverse events or deaths were reported.
At day 29, all participants vaccinated with SA4Ag achieved the CP5 opsonophagocytic activity (OPA) threshold (≥ 1,000 titers) and 96%–99% met the CP8 OPA threshold (≥ 2,000 titers).
“The percentage of subjects reaching the threshold is equivalent for each one of the vaccine doses, indicating that the rP305A did not affect the immune response to the other components in the vaccine,” Dr. Frenck Jr. said.
Less than 25% of patients given placebo achieved the CP5 or CP8 OPA thresholds.
Immune responses to ClfA were robust by day 15 and did not vary by the dose of rP305A, again suggesting that rP305A does not affect the other three antigens in the vaccine, he observed.
Immune responses to the rP305A antigen were dose dependent, with the percentage of patients with a threshold response increasing step-wise from the low (47%), mid (63.2%), and high (83%) doses.
By day 29, there was a very brisk rise in geometric mean titers for CP5. Responses did not differ by rP305A dose or across age groups, with a similar pattern observed for CP8 and ClfA, Dr. Fenck Jr. said.
Session co-moderator Dr. Walter Orenstein, from Emory University in Atlanta, commented that the rate of decay post-vaccination was promising, particularly compared with that observed with meningococcal vaccines.
The vaccine “program is exciting because it not only relies on just antibody, but it actually looks at functional responses and those functional responses have some correlate with protection against staphylococcal disease,” he said in an interview. High-risk populations, like renal dialysis patients, were not studied and it would be interesting to see how well they would respond. “Previous studies have shown transient benefits for those types of populations.”