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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Mucosal vaccine made from live, recombinant Lactococcus lactis protects mice against pharyngeal infection with
Praveen Mannam1, Kevin F Jones, Bruce L Geller
1Department of Microbiology, Oregon State University, Corvallis, Oregon 97330-3804, USA.
Abstract:
A novel vaccine (LL-CRR) made from live, nonpathogenic Lactococcus lactis that expresses the conserved C-repeat region (CRR) of M protein from Streptococcus pyogenes serotype 6 was tested in mice. Nasally vaccinated mice produced CRR-specific salivary immunoglobulin A (IgA) and serum IgG. Subcutaneously vaccinated mice produced CRR-specific serum IgG but not salivary IgA. A combined regimen produced responses similar to the salivary IgA of nasally vaccinated mice and serum IgG of subcutaneously vaccinated mice. Mice vaccinated nasally or with the combined regimen were significantly protected against pharyngeal infection following a nasal challenge with S. pyogenes M serotype 14. Mice vaccinated subcutaneously were not protected against pharyngeal infection. Mice in all three LL-CRR vaccination groups were significantly protected against the lethal effects of S. pyogenes. Only 1 of 77 challenged mice that were vaccinated with LL-CRR died, whereas 60 of 118 challenged mice that were vaccinated with a control strain or phosphate-buffered saline died. In conclusion, mucosal vaccination with LL-CRR produced CRR-specific salivary IgA and serum IgG, prevented pharyngeal infection with S. pyogenes, and promoted survival.
Insights
A novel vaccine using Lactococcus lactis expressing Streptococcus pyogenes C-repeat region (CRR) induced protective immunity. Nasal vaccination with LL-CRR prevented pharyngeal infection and enhanced survival against S. pyogenes.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Streptococcus pyogenes poses a significant public health threat, necessitating effective vaccines.
- Developing vaccines that elicit both mucosal and systemic immunity is crucial for preventing S. pyogenes infections.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of a novel vaccine (LL-CRR) against Streptococcus pyogenes.
Main Methods:
- A live Lactococcus lactis vaccine expressing the conserved C-repeat region (CRR) of S. pyogenes M protein was developed.
- Mice were vaccinated via nasal, subcutaneous, or combined routes, and immune responses (salivary IgA, serum IgG) were measured.
- Vaccine efficacy was assessed by challenging mice with S. pyogenes and monitoring for pharyngeal infection and survival.
Main Results:
- Nasal vaccination induced CRR-specific salivary IgA and serum IgG, while subcutaneous vaccination induced only serum IgG.
- Mice vaccinated nasally or with the combined regimen were protected against pharyngeal infection.
- All LL-CRR vaccination groups showed significant protection against lethal S. pyogenes challenge, with drastically reduced mortality compared to controls.
Conclusions:
- Mucosal vaccination with LL-CRR is effective in generating specific antibodies and preventing S. pyogenes pharyngeal infection.
- The LL-CRR vaccine demonstrates significant potential for protecting against lethal S. pyogenes infections.
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