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Updated: Sep 30, 2025
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
Antibiotic Treatment of Staphylococcus aureus Infection Inhibits the Development of Protective Immunity
Maureen Kleinhenz1, Pavani Beesetty1, Ching Yang1,2
1Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Abstract:
Recurrent Staphylococcus aureus infections are common, suggesting a failure to elicit protective immunity. Given the emergence of antibiotic resistance, a vaccine is urgently needed, but there is no approved vaccine for S. aureus. While antibiotics are routinely used to treat S. aureus infections, their impact on the development of protective immunity is not understood. Using an established mouse model of S. aureus skin and soft tissue infection (SSTI), we observed that antibiotic therapy effectively resolved infection but failed to elicit protection against secondary (2°) SSTI. Key contributors to protective immunity, toxin-specific antibodies and interleukin-17A (IL-17A)-producing T cells, were not strongly elicited in antibiotic-treated mice. Delaying antibiotic treatment failed to resolve skin lesions but resulted in higher antibody levels after infection and strong protection against 2° SSTI, suggesting that the development of protective immunity requires a longer period of antigen exposure. We next investigated if combining α-hemolysin (Hla) vaccination with antibiotics during primary infection would both treat infection and generate durable protective immunity. This "therapeutic vaccination" approach resulted in rapid resolution of primary infection and protection against recurrent infection, demonstrating that concurrent vaccination could circumvent the deleterious effects of antibiotic therapy on elicited immune responses. Collectively, these findings suggest that protective immunity is thwarted by the rapid elimination of antigen during antibiotic treatment. However, vaccination in conjunction with antibiotic treatment can retain the benefits of antibiotic treatment while also establishing protective immunity.
Insights
Antibiotic treatment for Staphylococcus aureus infections clears disease but prevents protective immunity. Combining antibiotics with vaccination during infection generates immunity and prevents recurrence.
Area of Science:
- Infectious Diseases
- Immunology
- Vaccinology
Background:
- Recurrent Staphylococcus aureus infections indicate a failure in protective immunity development.
- Antibiotic resistance necessitates an effective S. aureus vaccine, yet none are approved.
- The impact of antibiotics on protective immunity against S. aureus is unknown.
Purpose of the Study:
- To investigate the impact of antibiotic therapy on immune memory after S. aureus skin and soft tissue infection (SSTI).
- To determine if therapeutic vaccination can overcome antibiotic-induced immune suppression and confer protection against recurrent S. aureus SSTI.
Main Methods:
- A mouse model of S. aureus SSTI was used to compare outcomes of immediate antibiotic treatment, delayed antibiotic treatment, and therapeutic vaccination concurrent with antibiotics.
- Immune responses, including toxin-specific antibodies and IL-17A-producing T cells, were assessed.
- Protection against secondary S. aureus SSTI was evaluated.
Main Results:
- Antibiotic treatment resolved primary S. aureus SSTI but did not elicit protective immunity against secondary infections.
- Delayed antibiotic treatment led to incomplete lesion resolution but induced stronger protective immunity.
- Therapeutic vaccination, combining antibiotics with alpha-hemolysin (Hla) vaccination during primary infection, resolved infection and provided robust protection against recurrence.
Conclusions:
- Rapid antigen clearance by antibiotics during S. aureus infection impairs the development of protective immunity.
- Concurrent vaccination with antibiotics can effectively treat S. aureus infections while establishing durable protective immunity.
- Therapeutic vaccination represents a promising strategy to combat recurrent S. aureus infections and address antibiotic resistance.
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