Journal article
Immunity to Staphylococcus aureus secreted proteins protects rabbits from serious illnesses
Vaccine, Vol.30(34), pp.5099-5109
07/20/2012
DOI: 10.1016/j.vaccine.2012.05.067
PMCID: PMC3397198
PMID: 22691432
Abstract
► Vaccination against Staphylococcus aureus is achieved with toxoids. ► Toxoids are >107 inactivated and stimulate immunity to S. aureus. ► Superantigen toxoids exhibit adjuvant activity dependent on immune co-stimulatory molecule CD40 binding activity. ► Protective neutralizing antibodies are produced in rabbits to toxic shock syndrome toxin-1.
Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. This study investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. Importantly, 20% of humans and 50% of rabbits in our TSS model cannot generate antibody responses to native superantigens. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (β-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins β-toxin and γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity.
Details
- Title: Subtitle
- Immunity to Staphylococcus aureus secreted proteins protects rabbits from serious illnesses
- Creators
- Adam R Spaulding - Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USAYing-Chi Lin - Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USAJoseph A Merriman - Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USAAmanda J Brosnahan - Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USAMarnie L Peterson - Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USAPatrick M Schlievert - Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA
- Resource Type
- Journal article
- Publication Details
- Vaccine, Vol.30(34), pp.5099-5109
- DOI
- 10.1016/j.vaccine.2012.05.067
- PMID
- 22691432
- PMCID
- PMC3397198
- NLM abbreviation
- Vaccine
- ISSN
- 0264-410X
- eISSN
- 1873-2518
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AI074283, R01 AI73366, U54 AI57153
- Language
- English
- Date published
- 07/20/2012
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001147502771
Metrics
17 Record Views