Generation of specific effector and memory T cells with gut- and secondary lymphoid tissue- homing potential by oral attenuated CVD 909 typhoid vaccine in humans

Abstract

Induction of effective memory T cells is likely to be critical to the level and duration of protection elicited by novel live oral typhoid vaccines. Using cells from volunteers who ingested Salmonella Typhi vaccine strain CVD 909, we characterized the induction of interferon (IFN)-γ-secreting central (TCM, CD45RO+ CD62L+) and effector (TEM, CD45RO+ CD62L−) memory T populations, and their gut-homing potential based on integrin α4/β7 expression. Both CD4+ TEM and TCM populations secreted IFN-γ. However, although CD4+ TEM expressed, or not, integrin α4/β7, CD4+ TCM cells were predominantly integrin α4/β7+. In contrast, IFN-γ-secreting CD8+ cells were predominantly classical TEM and CD45RA+ TEM (TEMRA, CD45RO− CD62L−) subsets. However, although CD8+ TEM expressed, or not, integrin α4/β7, CD8+ TEMRA were predominantly integrin α4/β7+. This is the first demonstration that oral immunization of humans with S. Typhi elicits diverse IFN-γ-secreting CD4+ and CD8+ TCM and TEM subsets able to migrate to the gut and other lymphoid tissues.

Ex VivoKinetics of Early and Long-Term Multifunctional Human Leukocyte Antigen E-Specific CD8+Cells in Volunteers Immunized with the Ty21a Typhoid Vaccine

“…ϩ cells were predominantly classical T EM cells (41). Unexpectedly, these responses were multiphasic, with a first peak response observed as early as 4 days (in two out of five volunteers) after immunization ( Fig.…”

“…It is important to note that the level and timing of cytokine production varied among of the various volunteers. This is not surprising, since differences in the degree of response, as well as differences in the background level before immunization, among individuals are a common finding in human studies (32,40,41). Finally, as expected, only minor changes without defined patterns in cytokine secretion by S. Typhi-infected cells were observed in T NAÏVE cells or in the four subsets (T EM , T EMRA , T CM , and T NAIVE ) from two healthy volunteers used as controls in these studies (Fig.…”

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

“…Cross-protection may be due to humoral immune response cross-reactivity among LPS epitopes or common outer membrane proteins, such as OmpD, which has been shown to be a key target of protective antibodies (50). However, the protection can also be due to cross-reacting cell-mediated immune responses, which live oral Salmonella vaccines potently stimulate (51,52). There is evidence for cross-pro- tection in humans between certain typhoidal Salmonella serovars.…”

Waning Immunity and Microbial Vaccines—Workshop of the National Institute of Allergy and Infectious Diseases

“…Long-term multifunctional HLA-E-restricted CD8 ϩ cells coexpressing IFN-␥, tumor necrosis factor alpha (TNF-␣), and CD107 were also found (63). Interestingly, expression of homing molecules that direct these S. Typhi-specific central and effector memory T (T EM ) cell subsets to migrate to mucosal and nonmucosal tissues have also been reported (59,64).…”