Salmonella porins induce a sustained, lifelong specific bactericidal antibody memory response

Abstract

SummaryWe examined the ability of porins from Salmonella enterica serovar typhi to induce a long-term antibody response in BALB/c mice. These porins triggered a strong lifelong production of immunoglobulin G (IgG) antibody in the absence of exogenous adjuvant. Analysis of the IgG subclasses produced during this antibody response revealed the presence of the subclasses IgG2b, IgG1, IgG2a and weak IgG3. Despite the high homology of porins, the long-lasting anti-S. typhi porin sera did not cross-react with S. typhimurium. Notably, the antiporin sera showed a sustained lifelong bactericidal-binding activity to the wild-type S. typhi strain, whereas porin-specific antibody titres measured by enzyme-linked immunosorbent assay (ELISA) decreased with time. Because our porin preparations contained the outer membrane proteins C and F (OmpC and OmpF), we evaluated the individual contribution of each porin to the long-lasting antibody response. OmpC and OmpF induced long-lasting antibody titres, measured by ELISA, which were sustained for 300 days. In contrast, although OmpC induced sustained high bactericidal antibody titres for 300 days, postimmunization, the bactericidal antibody titre induced by OmpF was not detected at day 180. These results indicate that OmpC is the main protein responsible for the antibody-mediated memory bactericidal response induced by porins. Taken together, our results show that porins are strong immunogens that confer lifelong specific bactericidal antibody responses in the absence of added adjuvant.

Salmonella Induces a Switched Antibody Response without Germinal Centers That Impedes the Extracellular Spread of Infection

“…Thus, OMP, but not FliC or LPS, are major targets of this early EF, switched IgG2c Ab response. The capacity of OMP to induce Ab responses that can persist has been noted before (24). In conclusion, the EF plasma cell response against S. typhimurium is atypical in its early appearance, its size, and its longevity when compared with classical responses to Th2 alumprecipitated proteins (25).…”

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

“…Examples of adjuvants are oil emulsions [4][5][6], squalene (MF59) [7], immune stimulating complexes (ISCOMs [8,9]) with Quil-A and both gram-negative bacteria and bacterial products [4,[10][11][12]. These include DNA with immunostimulatory CpG motifs (one of the most powerful adjuvants [13]), Bordetella pertussis toxin [2,14], Corynebacterium granulosum derived P40 component [15], MPL [16], Mycobacterium and its components (Freund adjuvant) [4,17], Cholera toxin [18] and porins from various organisms such as Fusobacterium nucleatum [19], Shigella [20][21][22], Salmonella [22,23] and Neisseria meningitidis and gonorrhoeae [24][25][26][27][28][29].…”

“…Increased expression of CD86/CD80, MHC II and CD40 on the APC surface has been shown in response to porins from pathogenic Neisserial species (and other bacteria) [23,26,[30][31][32], as well as B cell proliferation and increased antibody production [33]. Activated APCs release specific cytokines (i.e.…”

IFN-γ–Producing CD4+ T Cells Promote Generation of Protective Germinal Center–Derived IgM+ B Cell Memory against Salmonella Typhi

“…Recent studies have established that a protective effect of antiSalmonella Abs in humans is due to their ability to facilitate complement-mediated lysis (18,20). Notably, Abs against porins (4,20) or against LPS (21) are associated with protective humoral immunity.…”

“…S. Typhi OmpC and OmpF can be purified and produced at large scale for application in humans (17). Such highly purified S. Typhi porins induce longlasting bactericidal Ab responses in mice (18) and exhibit intrinsic adjuvant activity (14,19). Intriguingly, S. Typhi porins have been applied to humans showing that this subunit vaccine is safe and immunogenic and that the B cell response in humans generates IgG and IgM Abs (17), suggesting that both isotypes could contribute to protection against this intracellular pathogen.…”