Dataset Information

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.

ABSTRACT: All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers ?4?7 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 ?4?7 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 (??=?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 ?/? 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.

SUBMITTER: Mwanza-Lisulo M

PROVIDER: S-EPMC6020133 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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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.

Mwanza-Lisulo Mpala M Chomba Mumba S MS Chama Mubanga M Besa Ellen C EC Funjika Evelyn E Zyambo Kanekwa K Banda Rose R Imikendu Mercy M Sianongo Sandie S Hancock Robert E W REW Lee Amy A Chilengi Roma R Stagg Andy J AJ Namangala Boniface B Kelly Paul M PM

Vaccine 20180522 28

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 resp ...[more]

PMID: 29801999

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Project description:BACKGROUND:In Zambia, cervical cancer screening was started in 2006 and the human papillomavirus vaccine was piloted in 2013. Nevertheless, cervical cancer remains the leading cancer. It is assumed that knowledge, social interaction, health behaviors and religion are factors that can influence screening and vaccination practices. This study addresses the question, what is the relationship between knowledge about cervical cancer, attitudes, self-reported behavior, and immediate support system, towards screening and vaccination of cervical cancer of Zambian women and men. The results of this study serve as a basis for future research, an input for improvement and adjustment of the existing prevention program and build on documented health behavior frameworks. METHODS:A cross-sectional mixed methods study was conducted from February to May 2016. Two separate questionnaires were used to collect data from women (N?=?300) and men (N?=?300) residing in Chilenje and Kanyama (two townships in the capital city Lusaka). Respondent's knowledge of cervical cancer was operationalized by grading their ability to correctly identify causes and protective factors if they were aware of cervical cancer. Besides providing descriptive statistics of all study variables, we tested four research hypotheses concerning the link between knowledge, attitudes and practices suggested by the literature, by applying appropriate statistical tests (chi square test, analysis of variance, logistic regression). RESULTS:Less than half of the respondents (36.8%) had heard of cervical cancer, 20.7% of women had attended screening and 6.7% of the total sample had vaccinated their daughter. Knowledge of causes and prevention was very low. There was a strong association between having awareness of cervical cancer and practicing screening (odds ratio?=?20.5, 95% confidence interval?=?[9.214, 45.516]) and vaccination (odds ratio?=?5.1, 95% confidence interval?=?[2.473, 10.423]). Social interactions were also found to greatly influence screening and vaccination behaviors. CONCLUSIONS:The low level of knowledge of causes and prevention of cervical cancer suggests a need to increase knowledge and awareness among both women and men. Interpersonal interactions have great impact on practicing prevention behaviors, for instance, vaccination of daughters.

Project description:Background and aimsROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia.MethodsWe conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose.ResultsThe study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period.ConclusionsAmong Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.

Dataset Information

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.

Publications

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.

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