Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines

Mpala Mwanza-Lisulo; Mumba S Chomba; Mubanga Chama; Ellen C Besa; Evelyn Funjika; Kanekwa Zyambo; Rose Banda; Mercy Imikendu; Sandie Sianongo; Robert E W Hancock; Amy Lee; Roma Chilengi; Andy J Stagg; Boniface Namangala; Paul M Kelly

doi:10.1016/j.vaccine.2018.04.083

Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines

Vaccine. 2018 Jun 27;36(28):4134-4141. doi: 10.1016/j.vaccine.2018.04.083. Epub 2018 May 22.

Authors

Affiliations

¹ Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia. Electronic address: [email protected].
² Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia.
³ Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Department of Chemistry, University of Zambia, Lusaka, Zambia.
⁴ University of British Columbia, Vancouver, Canada.
⁵ Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.
⁶ Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.
⁷ Institute of Distance Education, University of Zambia, Lusaka, Zambia.
⁸ Tropical Gastroenterology & Nutrition Group, Department of Medicine, School of Medicine, University of Zambia, Lusaka, Zambia; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK.

Abstract

All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4β7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4β7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/β signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.

Keywords: CCR9; Gut mucosa; Retinoic acid; Vaccines; α4β7.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage*
Administration, Oral
Adolescent
Adult
Animals
Cholera Vaccines / administration & dosage
Cholera Vaccines / immunology*
Gastrointestinal Tract / immunology*
Gene Expression Profiling
Healthy Volunteers
Humans
Immunoglobulin A / analysis
Immunologic Factors / biosynthesis
Integrins / analysis
Lipopolysaccharides / immunology
Male
Middle Aged
Polysaccharides, Bacterial / administration & dosage
Polysaccharides, Bacterial / immunology*
Receptors, CCR / analysis
Rotavirus Vaccines / administration & dosage
Rotavirus Vaccines / immunology*
T-Lymphocytes / chemistry
T-Lymphocytes / drug effects
T-Lymphocytes / immunology*
Tretinoin / administration & dosage*
Typhoid-Paratyphoid Vaccines / administration & dosage
Typhoid-Paratyphoid Vaccines / immunology*
Vaccines, Attenuated / administration & dosage
Vaccines, Attenuated / immunology
Young Adult
Zambia

Substances

Adjuvants, Immunologic
CC chemokine receptor 9
Cholera Vaccines
Dukoral
Immunoglobulin A
Immunologic Factors
Integrins
Lipopolysaccharides
Polysaccharides, Bacterial
RIX4414 vaccine
Receptors, CCR
Rotavirus Vaccines
Ty21a typhoid vaccine
Typhoid-Paratyphoid Vaccines
Vaccines, Attenuated
integrin alpha4beta7
Tretinoin