Abstract
Group B Streptococcus (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. Lactococcus lactis is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant L. lactis strain secreting SIP from GBS (rL. lactis-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with rL. lactis-SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our rL. lactis-SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naïve mice generated protection against GBS vaginal colonization. Moreover, the rL. lactis-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that rL. lactis-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.
Highlights
Group B Streptococcus (GBS), known as Streptococcus agalactiae, is a Gram-positive, facultative anaerobe and opportunist pathogen that is β-hemolytic on lamb blood agar
In relation to the molecular weight between surface immune protein (SIP) expressed in E. coli and rL. lactis-SIP, there is a small variation because SIP from E. coli contains a 6× histidine-tag and 25 amino acids of the signal peptide [12]
Compared to control animals that had higher body temperature. These results suggest that oral immunization with rSIP using rL. lactis-SIP provides a protective effect against the colonization of GBS, which was previously observed in oral immunization with recombinant SIP from
Summary
Group B Streptococcus (GBS), known as Streptococcus agalactiae, is a Gram-positive, facultative anaerobe and opportunist pathogen that is β-hemolytic on lamb blood agar. The global prevalence of maternal rectovaginal colonization is reported to be in the range of 11–35% [1,2,3]. There are no licensed vaccines for GBS, and phase I and II clinical trials are under way with hexavalent conjugate vaccines and protein-based vaccines [6,7]. Serotype-specific multivalent vaccines are being developed for delivery to pregnant women to protect their infants from GBS [6]. Polysaccharide-based vaccines induce an efficient protective immune response, such as partial coverage and induced escape, leading to persistence of disease [7]. GBS has been reported to have a capsular Switching from capsular polysaccharide (CPS) [8]. A vaccine based on a conserved and immunogenic protein could be an interesting alternative for the development of a vaccine against GBS [8]. A maternal vaccine given to pregnant women to stimulate the passive transplacental transfer of protective antibodies has the potential to reduce maternal disease, adverse pregnancy outcomes, and newborn disease [6,9]
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