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Start Over Descriptor "mucosal responses" Publisher oxford university press
2 results on '"mucosal responses"'

1. Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4+ T memory responses in humans

Author

Eric Goldberg, Bruce D. Greenwald, Jayaum S. Booth, Seema Patil, Marcelo B. Sztein, and Robin S. Barnes

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, lamina propria mononuclear cells, Ty21a, Immunology, Administration, Oral, chemical and pharmacologic phenomena, Peripheral blood mononuclear cell, complex mixtures, 03 medical and health sciences, 0302 clinical medicine, Interferon, Aldesleukin, blood, Ileum, CD4+ T, Immunology and Allergy, Medicine, Humans, Macrophage inflammatory protein, Immunity, Mucosal, Original Research, mucosal responses, business.industry, Polysaccharides, Bacterial, Typhoid-Paratyphoid Vaccines, Interleukin, General Medicine, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, 3. Good health, 030104 developmental biology, Immunization, bacteria, Interleukin 17, business, 030215 immunology, medicine.drug, typhoid fever
Abstract

Mucosal CD4+ T memory responses after typhoid immunization, Our current understanding of CD4+ T-cell-mediated immunity (CMI) elicited by the oral live attenuated typhoid vaccine Ty21a is primarily derived from studies using peripheral blood. Very limited data are available in humans regarding mucosal immunity (especially CD4+ T) at the site of infection (e.g. terminal ileum; TI). Here using multiparametric flow cytometry, we examined the effect of Ty21a immunization on TI-lamina propria mononuclear cells (LPMC) and peripheral blood CD4+ T memory (TM) subsets in volunteers undergoing routine colonoscopy. Interestingly, we observed significant increases in the frequencies of LPMC CD4+ T cells following Ty21a immunization, restricted to the T effector/memory (TEM)-CD45RA+ (TEMRA) subset. Importantly, Ty21a immunization elicited Salmonella Typhi-responsive LPMC CD4+ T cells in all major TM subsets [interferon (IFN)γ and interleukin (IL)-17A in TEM; IFNγ and macrophage inflammatory protein (MIP)1β in T central/memory (TCM); and IL-2 in TEMRA]. Subsequently, we analyzed LPMC S. Typhi-responsive CD4+ T cells in depth for multifunctional (MF) effectors. We found that LPMC CD4+ TEM responses were mostly MF, except for those cells exhibiting the characteristics associated with IL-17A responses. Finally, we compared mucosal to systemic responses and observed that LPMC CD4+S. Typhi-specific responses were unique and distinct from their systemic counterparts. This study provides the first demonstration of S. Typhi-specific CD4+ TM responses in the human TI mucosa and provides valuable information about the generation of mucosal immune responses following oral Ty21a immunization.

Published
2018

2. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens.

Author

Nyombayire J, Anzala O, Gazzard B, Karita E, Bergin P, Hayes P, Kopycinski J, Omosa-Manyonyi G, Jackson A, Bizimana J, Farah B, Sayeed E, Parks CL, Inoue M, Hironaka T, Hara H, Shu T, Matano T, Dally L, Barin B, Park H, Gilmour J, Lombardo A, Excler JL, Fast P, Laufer DS, and Cox JH

Subjects
AIDS Vaccines administration & dosage, AIDS Vaccines genetics, Administration, Intranasal, Adult, Female, Genes, Viral immunology, Genetic Vectors, HIV Antibodies blood, HIV Antibodies immunology, HIV Infections immunology, HIV-1 genetics, Humans, Immunity, Cellular, Immunity, Humoral, Immunization, Secondary, Immunogenicity, Vaccine, Kenya, Male, Middle Aged, Rwanda, Sendai virus immunology, Sendai virus physiology, United Kingdom, Vaccines, DNA administration & dosage, Virus Replication, AIDS Vaccines adverse effects, AIDS Vaccines immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections prevention & control, HIV-1 immunology, Sendai virus genetics, Vaccines, DNA adverse effects, Vaccines, DNA immunology
Abstract

Background:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine., Methods:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S L A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S H A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS H ); and priming and boosting with a higher-dose SeV-Gag given intranasally (S H S H )., Results:  All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S L A and S H A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8 + T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S L A and S H A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS H group. In contrast, the highest Gag-specific antibody titers were seen in the AS H group. Mucosal antibody responses were sporadic., Conclusions:  SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated., Clinical Trials Registration:  NCT01705990., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

Published
2017
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