Article

Live oral typhoid vaccine Ty21a induces cross-reactive humoral immune responses against Salmonella enterica serovar Paratyphi A and S. paratyphi B in humans. Clin Vaccine Immunol

Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.37). 04/2012; 19(6):825-34. DOI: 10.1128/CVI.00058-12
Source: PubMed

ABSTRACT Enteric fever caused by Salmonella enterica serovar Paratyphi A infection has emerged as an important public health problem. Recognizing that in randomized controlled field trials oral immunization with attenuated S. enterica serovar Typhi live vaccine Ty21a conferred significant cross-protection against S. Paratyphi B but not S. Paratyphi A disease, we undertook a clinical study to ascertain whether humoral immune responses could explain the field trial results. Ty21a immunization of adult residents of Maryland elicited predominantly IgA antibody-secreting cells (ASC) that recognize S. Typhi lipopolysaccharide (LPS). Cross-reactivity to S. Paratyphi A LPS was significantly lower than that to S. Paratyphi B LPS. ASC producing IgG and IgA that bind LPS from each of these Salmonella serovars expressed CD27 and integrin α4β7 (gut homing), with a significant proportion coexpressing CD62L (secondary lymphoid tissue homing). No significant differences were observed in serum antibody against LPS of the different serovars. Levels of IgA B memory (B(M)) cells to S. Typhi LPS were significantly higher than those against S. Paratyphi A or B LPS, with no differences observed between S. Paratyphi A and B. The response of IgA B(M) to outer membrane proteins (OMP) from S. Typhi was significantly stronger than that to OMP of S. Paratyphi A but similar to that to OMP of S. Paratyphi B. The percentages of IgG or IgA B(M) responders to LPS or OMP from these Salmonella strains were similar. Whereas cross-reactive humoral immune responses to S. Paratyphi A or B antigens are demonstrable following Ty21a immunization, they cannot explain the efficacy data gleaned from controlled field trials.

Download full-text

Full-text

Available from: Rezwanul Wahid, Jun 23, 2014
0 Followers
 · 
190 Views
  • Source
    • "Currently, two types of vaccines—oral live attenuated Salmonella Typhi Ty21a (Vivotif ® ) and the parenteral capsular Vi polysaccharide preparations (Typherix ® or Typhim Vi ® )—are available against typhoid fever, while none are licensed against paratyphoid or NTS serotypes. Interestingly, Ty21a and, to a lesser extent, the Vi vaccine have been shown to elicit cross-reactive immune responses against paratyphoid serotypes [3] [4] [5] [6] [7] [8] [9] and the most common NTS Salmonellae [10] [11]. The main underlying cause of cross-reactivity are the O-antigenic structures these strains share with S. Typhi: while S. Typhi expresses O-9,12, S. Paratyphi A and B carry the O-12, and many NTS Salmonellae express either O-9,12 (e.g. S. Enteritidis) or O-12 (e.g. S. Typhimurium). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since protective efficacy of the current typhoid vaccines—oral whole-cell Salmonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation—is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae, if administered concomitantly.
    Vaccine 11/2014; 33(3). DOI:10.1016/j.vaccine.2014.11.030 · 3.49 Impact Factor
  • Source
    • "Immunological memory is one of the key factors in the development of long-lasting immune responses to specific antigens (Levine and Sztein, 2004; Lanzavecchia et al., 2006; Simon et al., 2009, 2011; El-Kamary et al., 2010; Ramirez et al., 2012; Wahid et al., 2012). In the case of the B cell compartment, memory is generally accepted to be provided by two subpopulations: plasma cells and B M cells (Sanz et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Following interaction with cognate antigens, B cells undergo cell activation, proliferation and differentiation. Ligation of the B cell receptor (BCR) leads to the phosphorylation of BCR-associated signaling proteins within minutes of antigen binding, a process with profound consequences for the fate of the cells and development of effector immunity. Phosphoflow allows a rapid evaluation of various signaling pathways in complex heterogenous cell subsets. This novel technique was used in combination with multi-chromatic flow cytometry and fluorescent-cell barcoding to study phosphorylation of BCR-associated signaling pathways in naïve and memory human B cell subsets. Proteins of the initiation (Syk), propagation (Btk, Akt) and integration (p38MAPK and Erk1/2) signaling units were studied. Switched memory (Sm) CD27+ and Sm CD27- phosphorylation patterns were similar when stimulated with anti-IgA or -IgG. In contrast, naïve and unswitched memory (Um) cells showed significant differences following IgM stimulation. Enhanced phosphorylation of Syk was observed in Um cells, suggesting a lower activation threshold. This is likely the result of higher amounts of IgM on the cell surface, higher pan-Syk levels and enhanced susceptibility to phosphatase inhibition. All other signaling proteins evaluated also showed some degree of enhanced phosphorylation in Um cells. Furthermore, both the PLC-γ2 and PI3K pathways were activated in Um cells, while only the PI3K pathway was activated on naïve cells. Um cells were the only ones that activated signaling pathways when stimulated with fluorescently-labeled S. Typhi and S. pneumoniae. Finally, simultaneous evaluation of signaling proteins at the single cell level (multi-phosphorylated cells) revealed that interaction with gram positive and negative bacteria resulted in complex and diverse signaling patterns. Phosphoflow holds great potential to accelerate vaccine development by identifying signaling profiles in good/poor responders.
    Frontiers in Cellular and Infection Microbiology 10/2012; 2:128. DOI:10.3389/fcimb.2012.00128 · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review summarizes the recent advances in vaccination against Salmonella enterica serovar Typhi and highlights the data supporting the development of next generation vaccines to address paratyphoid fever and invasive nontyphoidal Salmonella (iNTS) disease. There has been increasing awareness of the disease burden caused by S. Typhi particularly in Africa and greater recognition of S. Paratyphi A's contribution to enteric fever episodes throughout Asia. Groups have been working to improve the existing typhoid vaccines and provide comprehensive data on the feasibility of their implementation in endemic settings. These data have resulted in modifications to the recommendations for typhoid vaccination in traveller markets and endemic settings, and has also led to the development of S. Paratyphi A vaccine components that can be combined with existing typhoid vaccines to generate bivalent formulations against enteric fever. The epidemiology of iNTS serovars as cause of appreciable morbidity and mortality in Africa, and the need for vaccines, has also become more widely appreciated. Current typhoid vaccines, although moderately effective for short periods of time, cannot be used in all age groups and only target one of the clinically relevant Salmonella serovars. Greater effort must be placed on the development and implementation of improved vaccines for the disease burden resulting from Typhi, Paratyphi A or iNTS infections.
    Current Opinion in Infectious Diseases 07/2012; 25(5):489-99. DOI:10.1097/QCO.0b013e328356ffeb · 5.03 Impact Factor
Show more