Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection

Abstract

Streptococcus pneumoniae is a major respiratory mucosal pathogen affecting infants and children. Although a polysaccharide-based vaccine has been useful in adult populations, it does not elicit protective immunity in infants and young children. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein produced by all strains of Streptococcus pneumoniae. Previous studies have shown that systemic immunization of mice with PspA can elicit protective immunity against fatal pneumococcal infection. In this study, we demonstrated that oral immunization with PspA could elicit protective immune responses against pneumococcal infection. When mice were orally immunized with PspA alone, low levels of PspA-specific immunoglobulin G (IgG) responses were induced in serum; none was induced in secretion. On the other hand, when PspA was given orally with the mucosal adjuvant cholera toxin (CT), significant levels of IgG and IgA anti-PspA responses were induced in serum. The major IgG subclass was IgG1, followed by IgG2b, a profile of antibody response supported by Th2-type cells. In addition, all mice orally immunized with PspA and CT were protected from the lethal challenge with capsular serotype 3 S. pneumoniae A66. These results suggested that an oral PspA vaccine may be a useful means of preventing pneumococcal disease.

Transcutaneous immunization with an outer membrane protein of Porphyromonas gingivalis without adjuvant elicits marked antibody responses

“…Since mucosal (e.g. nasal or oral) administration of CT with soluble protein has proven to be an effective regimen for the generation of antigen‐specific antibody responses (20, 28, 30, 45, 47), we next examined the effect of the transcutaneous administration of CT as adjuvant on 40 K‐OMP‐specific antibody responses. Rats transcutaneously immunized with 40k‐OMP plus CT showed almost the same 40k‐OMP‐specific serum IgG and IgA responses as those immunized with 40k‐OMP alone (Fig.…”

“…It is important to note that TCI with 40k‐OMP alone elicited significant serum responses as well as salivary IgG responses. Normally, protein antigen given via the mucosal route without adjuvant has been generally reported to be only a weak immunogen (28, 45–47) and therefore, has been presumed to require a mucosal adjuvant such as CT to induce antigen‐specific antibody responses (28, 31, 45, 47). Our previous findings also indicated that nasal delivery of 40k‐OMP with CT as an adjuvant induced 40k‐OMP‐specific Th2‐type responses that in turn led to the induction of serum IgG and IgA as well as salivary IgA antibodies (30, 31).…”

“…The mononuclear cells were obtained at the interface of the 50 and 75% layers of a discontinuous Percoll gradient (Amersham Pharmacia Biotech, Piscataway, NJ). To assess the numbers of antigen‐specific AFCs, an ELISPOT assay was performed as previously described (47). Briefly, 96‐well nitrocellulose plates (Millititer HA; Millipore Cop., Bedford, MA) were coated with 40k‐OMP (5 μg/ml), incubated for 20 h at 4°C, washed extensively and blocked with RPMI‐1640 containing 10% fetal calf serum.…”

Sublingual vaccination with fusion protein consisting of the functional domain of hemagglutinin A of Porphyromonas gingivalis and Escherichia coli maltose-binding protein elicits protective immunity in the oral cavity

“…Mononuclear cells were obtained at the interface of the 50% and 75% layers of a discontinuous Percoll gradient (GE Healthcare UK, Ltd, Little Chalfont, Buckinghamshire, UK) (Maeba et al ., ). To assess the numbers of antigen‐specific AFCs, an enzyme‐linked immunospot (ELISPOT) assay was performed as described previously (Yamamoto et al ., ). Briefly, 96‐well nitrocellulose plates (BD Biosciences, Franklin Lakes, NJ) were coated with 25k‐hagA‐MBP (5 μg mL −1 ), incubated at 4 °C for 20 h, and then washed extensively before being blocked with RPMI‐1640 containing 10% fetal calf serum.…”

“…Previous studies have demonstrated the efficacy of mucosal immunization for delivering vaccines, which induces mucosal and systemic immune responses via oral (Yamamoto et al ., ; Liu et al ., ), nasal (Koizumi et al ., ; Momoi et al ., ), and sublingual routes (Cuburu et al ., ; Song et al ., ; Zhang et al ., ). Of the vaccination methods available, sublingual vaccination has recently been reported to induce significant antibody (Ab) production in nasal, bronchial, and oral mucosa (Cuburu et al ., ; Zhang et al ., ).…”