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Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes
Rasmus Mortensen1,2, Dennis Christensen1, Lasse Bøllehuus Hansen3
1Statens Serum Institut, Department of Infectious Disease Immunology, Copenhagen, Denmark.
Abstract:
Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.
Insights
Local immunity is crucial for protecting against Streptococcus pyogenes (group A streptococcus, GAS) respiratory infections. Parenteral vaccines induce systemic immunity but fail to protect against intranasal GAS, highlighting the need for mucosal vaccination strategies.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Streptococcus pyogenes (group A streptococcus, GAS) causes diverse infections, commonly transmitted via respiratory droplets.
- Understanding vaccine-induced immunity relative to administration route is vital for developing effective GAS vaccines.
Purpose of the Study:
- To investigate if parenteral vaccination confers protection against intranasal GAS infection.
- To determine if locally primed immunity is required for protection against intranasal GAS challenge.
Main Methods:
- A CAF01-adjuvanted GAS vaccine was administered parenterally or intranasally in a murine model.
- Mice were challenged intranasally or intraperitoneally with GAS.
- Immune responses (systemic and mucosal) were assessed.
Main Results:
- Parenteral vaccination induced strong systemic immunity and protected against intraperitoneal GAS infection but not intranasal infection.
- Intranasal vaccination induced protection against repeated intranasal GAS infections.
- Lack of protection from parenteral vaccination correlated with reduced mucosal immune recall at the infection site.
Conclusions:
- Locally primed mucosal immunity is essential for effective defense against intranasal Streptococcus pyogenes infections.
- Route of vaccine administration significantly impacts protective immunity against GAS, particularly for respiratory pathogens.