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A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A
M Yamamoto1, D E Briles, S Yamamoto
1Department of Oral Biology, University of Alabama Medical Center, Birmingham 35294, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 21, 1998
Summary
Intranasal administration of pneumococcal surface protein A (PspA) with a cholera toxin mutant (mCT) S61F vaccine effectively protects against Streptococcus pneumoniae. This mucosal vaccine induces robust antibody and CD4+ T cell responses, crucial for combating pneumococcal infections.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Pneumococcal surface protein A (PspA) is a key virulence factor of Streptococcus pneumoniae.
- Developing effective mucosal vaccines against pneumococcal infections remains a significant public health challenge.
- Cholera toxin (CT) and its derivatives are known for their adjuvant properties in mucosal immunization.
Purpose of the Study:
- To evaluate the efficacy of intranasal administration of PspA combined with a nontoxic mutant of cholera toxin (mCT) S61F as a mucosal vaccine.
- To assess the induced systemic and mucosal immune responses, including antibody and T cell profiles.
- To determine the protective efficacy against lethal challenge with Streptococcus pneumoniae.
Main Methods:
- Mice were immunized intranasally with PspA and mCT S61F.
- PspA-specific IgG and IgA antibody levels in serum, spleen, cervical lymph nodes (CLN), lung tissue, saliva, and nasal secretions were measured.
- Cytokine production and CD4+ T cell responses (IL-4, IFN-gamma) were analyzed.
- Mice were challenged with a lethal dose of Streptococcus pneumoniae to assess protection.
Main Results:
- Intranasal PspA plus mCT S61F significantly increased PspA-specific IgG and IgA antibodies in serum and mucosal secretions.
- Higher levels of anti-PspA antibody-forming cells were observed in spleens, CLN, and lung tissue compared to non-immunized controls.
- The adjuvant effect of mCT S61F was crucial for these responses, which were comparable to native CT (nCT).
- PspA-specific CD4+ T cells producing IL-4 (Th2 response) were enhanced in CLN.
- Immunized mice showed significant protection against lethal Streptococcus pneumoniae challenge.
Conclusions:
- Intranasal administration of PspA with mCT S61F serves as an effective mucosal vaccine against pneumococcal infection.
- The vaccine induces protective systemic and mucosal antibody responses and Th2-biased CD4+ T cell immunity.
- mCT S61F acts as a potent mucosal adjuvant, facilitating robust immune responses to PspA.