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*
Immunobiology Vaccine Center, Departments of Oral Biology and Microbiology, University of Alabama Medical Center, Birmingham, AL 35294; and
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
In this study, we demonstrated that pneumococcal surface protein A
(PspA) nasally administered with a nontoxic A subunit mutant of cholera
toxin (mCT) S61F elicited a protective immune response. Immunization
with PspA and mCT elicited higher levels of PspA-specific IgG and IgA
Abs in serum and of IgG and IgA anti-PspA Ab-forming cells in
spleens, cervical lymph nodes (CLN), and lung tissue when compared to
nonimmunized mice. Furthermore, significant PspA-specific IgA Abs were
induced in saliva and nasal secretions. These responses were dependent
on the use of mCT as a mucosal adjuvant. The PspA-specific Ab responses
induced by mCT S61F were comparable with those induced by native CT
(nCT). Analysis of cytokine responses showed that nasal PspA plus mCT
S61F enhanced the induction of PspA-specific CD4+ T cells
producing IL-4 but not IFN-
in CLN at both the protein and mRNA
levels. Importantly, significant numbers of mice intranasally immunized
with PspA plus mCT S61F were protected from lethal challenge with
capsular serotype 3 Streptococcus pneumoniae A66. These
results show that intranasal administration of PspA together with mCT
S61F is an effective mucosal vaccine against pneumococcal infection and
induces CD4+ Th2-type cells, which provide help for both
mucosal and systemic Ab responses.
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