Nasal immunization of mice withLactobacillus caseiexpressing the pneumococcal surface protein C primes the immune system and decreases pneumococcal nasopharyngeal colonization in mice

Abstract

Streptococcus pneumoniae colonizes the upper respiratory tract of healthy individuals, from where it can be transmitted to the community. Occasionally, bacteria invade sterile niches, causing diseases. The pneumococcal surface protein C (PspC) is a virulence factor that is important during colonization and the systemic phases of the diseases. Here, we have evaluated the effect of nasal or sublingual immunization of mice with Lactobacillus casei expressing PspC, as well as prime-boosting protocols using recombinant PspC, on nasopharyngeal pneumococcal colonization. None of the protocols tested was able to elicit significant levels of anti-PspC antibodies before challenge. However, a significant decrease in pneumococcal recovery from the nasopharynx was observed in animals immunized through the nasal route with L. casei-PspC. Immune responses evaluated after colonization challenge in this group of mice were characterized by an increase in mucosal anti-PspC immunoglobulin A (IgA) 5 days later, a time point in which the pneumococcal loads were already low. A negative correlation between the concentrations of anti-PspC IgA and pneumococcal recovery from the nasopharynx was observed, with animals with the lowest colonization levels having higher IgA concentrations. These results show that nasal immunization with L. casei-PspC primes the immune system of mice, prompting faster immune responses that result in a decrease in pneumococcal colonization.

Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium

“…route in mice has been described, especially for animal models of allergy (44,65,66). However, the use of this route for vaccination, using recombinant lactic acid bacteria expressing heterologous antigens, has been less explored (22).…”

Oral immunization of mice against Clostridium perfringens epsilon toxin with a Lactobacillus casei vector vaccine expressing epsilon toxoid

“…This vector contained a spaX gene product as an anchor to express antigens on the cell wall. The spaX is considered a good choice for surface expressing in L. casei [19,29]. Meanwhile, the expression of susceptible antigens for mucosal immunization with live vectors can elicit a better immune response when the expressed proteins anchor to a cell wall [10,32,38].…”

“…The pellets were suspended in a lysis buffer (50 mM Glucose, 25 mM Tris-HCl, 10 mM EDTA, 20 mg/ml Lysozyme, pH 8.0) and exposed to three consecutive freeze-thaw cycles. The protein fractions were processed as previously described [29,30].…”

Engineering commensal bacteria for prophylaxis against infection

“…Attenuated pathogens or LAB have been engineered to function as vaccine delivery vehicles against pathogens including Yersinia pseudotuberculosis [27], Salmonella Typhimurium [28,29], and Pneumococcal nasopharyngeal [30,31]. One particular study by Mohamadzadeh et al showed that a recombinant LAB vaccine could be as effective as a traditional injected vaccine in an animal model [32•].…”