Comparative analysis of immunological responses to oral (Ty21a) and parenteral (TAB) typhoid vaccines

D’Amelio, Raffaele; Tagliabue, Aldo; Nencioni, L; Addario, Antonio; Villa, L; Manganaro, Mario; Boraschi, Diana; Moli, S. Le; Nisini, Roberto; Matricardi, Paolo Maria

doi:10.1128/iai.56.10.2731-2735.1988

Cited by 43 publications

(18 citation statements)

References 15 publications

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“…In agreement with this hypothesis, Salmonella ‐specific T‐cell responses are detected in Ty21a‐immunized patients . Ab responses are also induced by immunization with live attenuated Salmonella vaccines, but the role of these Abs in protective immunity is less clear . The generation of improved vaccines for typhoid and NTS will require a deeper understanding of adaptive immunity to Salmonella infection and greater knowledge of how this pathogen is able to subvert protective responses.…”

Section: Introductionmentioning

confidence: 89%

“…In contrast to the ViCPS vaccine, the protection mediated by the live attenuated Ty21a vaccine is thought to require the induction of T‐cell‐mediated immunity . In agreement with this hypothesis, Salmonella ‐specific T‐cell responses are detected in Ty21a‐immunized patients . Ab responses are also induced by immunization with live attenuated Salmonella vaccines, but the role of these Abs in protective immunity is less clear .…”

Section: Introductionmentioning

confidence: 99%

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Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

et al. 2014

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CD4+ T cells and B cells are both essential for acquired immunity to Salmonella infection. It is well established that Salmonella inhibit host CD4+ T-cell responses, but a corresponding inhibitory effect on B cells is less well defined. Here, we utilize an antigen tetramer and pull-down enrichment strategy to directly visualize OVA-specific B cells in mice, as they respond to infection with Salmonella-OVA. Surprisingly, OVA-specific B-cell expansion and germinal center formation was not detected until bacteria were cleared from the host. Furthermore, Salmonella infection also actively inhibited both B- and T-cell responses to the same coinjected antigen but this did not require the presence of iNOS. The SPI2 locus has been shown to be responsible for inhibition of Salmonella-specific CD4+ T-cell responses, and an examination of SPI2-deficient bacteria demonstrated a recovery in B-cell expansion in infected mice. Together, these data suggest that Salmonella can simultaneously inhibit host B- and T-cell responses using SPI2-dependent mechanisms.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

et al. 2014

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“…Oral Ty21a vaccine stimulates strong CMI responses, including T-cell proliferation, secretion of Th1-type cytokines (e.g. IFN-c and TNF-a) (88,90,95,97) and classical class Iarestricted as well as non-classical class-Ib HLA-E-restricted CD8 + CTLs (87)(88)(89)(90). Previous studies in humans have demonstrated a relationship between the presence of multifunctional T cells (capable of producing multiple cytokines) and the quality of the immune responses (98,99).…”

Section: Live Oral Typhoid Vaccine (Ty21a)mentioning

confidence: 99%

Immunology of gut mucosal vaccines

Pasetti¹,

Simon

Sztein

et al. 2010

Immunological Reviews

210

142

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SummaryUnderstanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines.

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“…Following oral administration, live attenuated Salmonella spp. vaccines can elicit protective immunity associated with the induction of mucosal and serum antibodies as well as a T-cell response (1,7,9,23,24,27).…”

mentioning

confidence: 99%

Mucosal and Systemic Immune Responses in Humans after Primary and Booster Immunizations with Orally Administered Invasive and Noninvasive Live Attenuated Bacteria

et al. 1999

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The mucosal and systemic immune responses after primary and booster immunizations with two attenuated live oral vaccine strains derived from a noninvasive (Vibrio cholerae) and an invasive (Salmonella typhi) enteric pathogen were comparatively evaluated. Vaccination with S. typhi Ty21a elicited antibody-secreting cell (ASC) responses specific for S. typhi O9, 12 lipopolysaccharide (LPS), as well as significant increases in levels of immunoglobulin G (IgG) and IgA antibodies to the same antigen in serum. A strong systemic CD4+ T-helper type 1 cell-mediated immune (CMI) response was also induced. In contrast to results with Ty21a, no evidence of a CMI response was obtained after primary immunization with V. cholerae CVD 103-HgR in spite of the good immunogenicity of the vaccine. Volunteers who received a single dose of CVD 103-HgR primarily developed an IgM ASC response against whole vaccine cells and purified V. cholerae Inaba LPS, and seroconversion of serum vibriocidal antibodies occurred in four of five subjects. Serum IgG anti-cholera toxin antibody titers were of lower magnitude. For both live vaccines, the volunteers still presented significant local immunity 14 months after primary immunization, as revealed by the elevated baseline antibody titers at the time of the booster immunization and the lower ASC, serum IgG, and vibriocidal antibody responses after the booster immunization. These results suggest that local immunity may interfere with colonization of the gut by both vaccine strains at least up to 14 months after basis immunization. Interestingly, despite a low secondary ASC response, Ty21a was able to boost both humoral (anti-LPS systemic IgG and IgA) and CMI responses. Evidence of a CMI response was also observed for one of three volunteers given a cholera vaccine booster dose. The direct comparison of results with two attenuated live oral vaccine strains in human volunteers clearly showed that the capacity of the vaccine strain to colonize specific body compartments conditions the pattern of vaccine-induced immune responses.

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Comparative analysis of immunological responses to oral (Ty21a) and parenteral (TAB) typhoid vaccines

Cited by 43 publications

References 15 publications

Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

Direct visualization of endogenous Salmonella‐specific B cells reveals a marked delay in clonal expansion and germinal center development

Immunology of gut mucosal vaccines

Mucosal and Systemic Immune Responses in Humans after Primary and Booster Immunizations with Orally Administered Invasive and Noninvasive Live Attenuated Bacteria

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