S. aureus disease affects many patient populations and results in diverse clinical presentations
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MRSA=methicillin-resistant Staphylococcus aureus; MSSA=methicillin-sensitive Staphylococcus aureus. 1. Foster T. Staphylococcus. In: Baron S, ed. Medical Microbiology. Galveston, TX: University of Texas Medical Branch at Galveston; 1996. 2. Liu C et al. Clin Infect Dis 2011;52:285-292. 3. Styers D et al. Ann Clin Micro Antimicrob 2006;5:2. 4. Kuehnert MJ et al. J Infect Dis 2006;193:172-179. 5. von Eiff C et al. N Engl J Med. 2001;344:11-16. 6. Hersh AL et al. Arch Intern Med. 2008;168:1585–1591. 7. Centers for Disease Control and Prevention. MRSA and the workplace [updated 19 September 2014]. Available from: http://www.cdc.gov/niosh/topics/mrsa/. 8. Laupland KB et al. J Infect Dis. 2003;187:1452-1459. 9. National Nosocomial Infections Surveillance System. Am J Infect Control 1996;24(5):380-388. 10. Eili Klein*, David L. Smith†, and Ramanan Laxminarayan. Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005. Volume 13, Number 12—December 2007 Research. 11. Koeck et al, Invasive Staphylococcus aureus Infections in Minnesota: A Large Role for MSSA. IDWeek 2015 12. CDC. 2014. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Methicillin-Resistant Staphylococcus aureus, 2014. Available via the Internet: http://www.cdc.gov/abcs/reports-findings/survreports/mrsa14.html 13. CDC data (Scott Fridkin/CDC) (June 7, 2016)
S. aureus Vaccine (SA4Ag) is Designed To Target Multiple Virulence Mechanisms
Virulence Mechanism |
Target Antigens |
Functional Immunoassay(s) |
|---|---|---|
| Anti-phagocytic | Capsular polysaccharides (CP5 and CP8): CP5-CRM197, CP8-CRM197 | OPA cLIA |
| Adhesion to host factors | Clumping factor A (ClfA): rmClfA | FBI cLIA |
| Divalent cation scavenging (nutrient acquistion) | Manganese transporter C (MntC): rP305A | cLIA |
- Selected antigens elicit immune responses targeting surface-expressed, conserved, and globally represented S. aureus components expressed during infection
- Being investigated to determine if it’s broadly protective across the range of clinical S. aureus disease isolates regardless of their antibiotic resistance profiles or geographic origin
1 Nanra JS, et al. Hu Vacc Immunotherapeutics 2013; 9(3):480-7;
2 Rozemeijer W, et al. ICAAC 2012 (G-870);
3 Hawkins J, et al. Clin Vacc Immunology 2012; 19(10):1641-50
2 Rozemeijer W, et al. ICAAC 2012 (G-870);
3 Hawkins J, et al. Clin Vacc Immunology 2012; 19(10):1641-50
SA4Ag Clinical Development Program to Date
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1. Nissen M, et al. Vaccine. 2015;33(15):1846-54 (Clinicaltrials.gov: NCT01018641). 2. Frenck RW Jr., et al. Open Forum Infect Dis (Fall 2014) 1 (suppl 1):S25. Oral presentation at IDWeek; Oct 8–12, 2014; Philadelphia, PA, USA (Clinicaltrials.gov: NCT01364571). 3. Scully et al. Surg Infect (Larchmt). 2015;16 (Suppl 1):S-30. Poster presentation at the Surgical Infection Society-35th Annual Meeting; Apr 15–18, 2015; Westlake Village, CA, USA (Clinicaltrials.gov: NCT01364571). 4. Creech CB, et al. Open Forum Infect Dis (Fall 2015) 2 (suppl 1):S36. Oral presentation at IDWeek; Oct 7–11, 2015; San Diego, CA, USA (Clinicaltrials.gov: NCT01643941). 5. Begier E, et al. Poster presentation at the Surgical Infection Society-36th Annual Meeting; May 18–21, 2016; Palm Beach, FL, USA (Clinicaltrials.gov: NCT02364596). 6. Study ongoing (Clinicaltrials.gov: NCT02492958). 7. Study ongoing (Clinicaltrials.gov: NCT02388165).
SA4Ag Elicits a Rapid and Sustained Immune Response through Month 12
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*SA4Ag includes 30 µg of CP5-CRM197, 30 µg of CP8-CRM197, 60 µg of rmClfA, and 200 µg of rP305A (MntC)
Injection Site Reactions (adults 18 to <65 yrs)
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- Reactions at injection site were generally mild to moderate in severity and lasted 1-3 days
- Onset usually within first 3 days
- Severe reactions required no specific treatment, lasted a few days
Injection Site Reactions (adults 65 to <86 years)
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- Reactions at injection site were mostly mild and generally lasted 1-4 days
- Onset usually within first 3 days
- Several subjects reported onset of local reactions around Day 7, almost all resolved by Day 10.
Systemic Events (adults 18 to <65 years)
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- Systemic events reported in e-diary through 14 days after vaccination;
- B3451001 study in healthy adults aged 18 to <65 years, placebo and high dose SA4Ag groups
- General symptoms were similar in those who received SA4Ag and placebo
Systemic Events (adults 65 to <86 years)
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- Systemic events reported in e-diary through 14 days after vaccination;
- B3451011 study in healthy adults aged 65 to <86 years, placebo and high dose SA4Ag groups
- General symptoms were similar in those who received SA4Ag and placebo
Phase 1/2a: Summary and Conclusions
- > 1,000 healthy subjects have received Pfizer’s investigational S. aureus vaccine in Phase 1/2 clinical trials to date
- SA4Ag was generally well tolerated, with no safety concerns in healthy adults 18 to <86 years
- A single dose of SA4Ag induces a rapid rise in bacteria-killing antibodies that is sustained through at least 12 months after vaccination in healthy adults 18 to <86 years
- The STRIVE study (B3451002) is being conducted in patients undergoing elective open posterior instrumented spinal fusion procedures to further evaluate the safety and efficacy of SA4Ag