Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses.

Introduction: Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood. Methods and results: Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV. Discussion: Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.

Salmonella infection induces the reorganization of follicular dendritic cell networks concomitant with the failure to generate germinal centers.

Germinal centers (GCs) are sites where plasma and memory B cells form to generate high-affinity, Ig class-switched antibodies. Specialized stromal cells called follicular dendritic cells (FDCs) are essential for GC formation. During systemic Salmonella Typhimurium (STm) infection GCs are absent, whereas extensive extrafollicular and switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we demonstrate that STm induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone. Alongside these effects after infection, mature FDC networks are strikingly absent, whereas immature FDC precursors, including marginal sinus pre-FDCs (MadCAM-1+) and perivascular pre-FDCs (PDGFRß+) are enriched. As normal FDC networks re-establish, extensive GCs become detectable throughout the spleen. Therefore, the reorganization of FDC networks and the loss of GC responses are key, parallel features of systemic STm infections.

Outer membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface.

Lipopolysaccharide (LPS) O-antigen (O-Ag) is known to limit antibody binding to surface antigens, although the relationship between antibody, O-Ag and other outer-membrane antigens is poorly understood. Here we report, immunization with the trimeric porin OmpD from Salmonella Typhimurium (STmOmpD) protects against infection. Atomistic molecular dynamics simulations indicate this is because OmpD trimers generate footprints within the O-Ag layer sufficiently sized for a single IgG Fab to access. While STmOmpD differs from its orthologue in S. Enteritidis (SEn) by a single amino-acid residue, immunization with STmOmpD confers minimal protection to SEn. This is due to the OmpD-O-Ag interplay restricting IgG binding, with the pairing of OmpD with its native O-Ag being essential for optimal protection after immunization. Thus, both the chemical and physical structure of O-Ag are key for the presentation of specific epitopes within proteinaceous surface-antigens. This enhances combinatorial antigenic diversity in Gram-negative bacteria, while reducing associated fitness costs.

Prevalence and characterization of occult hepatitis B infection among blood donors in central Saudi Arabia.

OBJECTIVES: To evaluate the prevalence of occult hepatitis B viral infections (OBIs)  among blood donors considering the clinical and epidemiological importance of identifying OBIs. METHODS: A cross-sectional study conducted at King Khalid University Hospital, Riyadh, Saudi Arabia between January 2011 and January 2012. Blood donors (n=8501) were screened for Hepatitis B virus surface antigen (HBsAg) and hepatitis B core antibodies (HBcAb). All HBsAg-negative and HBcAb-positive samples were tested further for hepatitis B surface antibodies (HBsAb), hepatitis B virus (HBV)-DNA, and HBV genotyping.   RESULTS: Of the 8501 serum samples tested, 56 (0.7%) were positive and 8445 (99.3%) were negative for HBsAg. Among the HBsAg-negative samples, 198 (2.3%) were positive for HBcAb and these patients were suspected to have OBIs. Among the HBcAb-positive samples, 119 (60.1%) were positive while 79 (39.9%) were negative for HBsAb. Analysis of HBV-DNA for the suspected OBIs showed that 17 out of 198 samples (8.6%) yielded positive results, and all of them were HBsAb-negative. The viral load was low (less than 20-186 IU/mL) in all OBIs. Hepatitis B virus genotyping showed that 15 out of 17 samples (88.2%) were genotype D, and the other 2 samples (11.8%) were genotype E.  CONCLUSION: The prevalence of OBIs among blood donors in Riyadh was 0.2%. Therefore, it is recommended that HBV molecular testing should be incorporated with serological assays for screening of blood donors.