Investigation of Serious Adverse Events Following Vaccination Against Yellow Fever: Emphasis on Genetic Basis and Biological Markers

It concerns an investigation aiming to investigate genetic biological(s) marker(s) which allow to identify individuals who have risk of serious adverse events to the yellow fever vaccine. This testing is free of hypothesis, because these markers are still unknown. There is no intervention, and it is not possible to establish primary and secondary outcomes.

Study Overview

• Status: Recruiting
• Conditions: Drug-Related Side Effects and Adverse Reactions

Detailed Description

The rational for the immunological study by LATIM is the observation made by the group that individuals vaccinated with the 17DD yellow fever vaccine show significant alterations on the levels of expression of genes such as CLEC5A, IFNG, IL6, RNASEL, IRF7, IRF9, STAT2 e OAS1 (8). The study which will be conducted by the Rockefeller University will be focused in the qualitative analysis of the genome and exome of volunteers. The study in LATIM will be focused in the quantitative analysis of mRNA, which, together with the results of sequencing, may help in the search for biomarkers. As the expression of mRNA is restricted to the acute phase of the adverse event, it will be done only during the first 30 days after the beginning of the adverse event.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Jean-Laurent Casanova, PhD; Phone Number: +1 212 3277332; Email: casanova_studies@rockefeller.edu
• Study Contact Backup: Name: Patricia MN de Oliveira, MD, PhD; Phone Number: 552138827000; Email: patricia.mouta@bio.fiocruz.br

Study Locations

• Brazil
  • RJ
    • Rio De Janeiro, RJ, Brazil, 21.040-360
      • Recruiting
      • Assessoria Clinica / Bio-Manguinhos / Fiocruz
      • Contact: Patricia MN de Oliveira, MD, PhD; Phone Number: 552138827000; Email: patricia.mouta@bio.fiocruz.br
      • Principal Investigator: Patricia MN de Oliveira, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 59 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will recruit cases of severe adverse event after yellow fever vaccine.

Description

Inclusion criteria:

• Evidence of a systemic reaction in two or more organs within one month of vaccination with yellow fever vaccine;
• Laboratory evidence of yellow fever vaccine virus (at least one):

Positive culture for more than 7 days after vaccination; RT-PCR ≥ 3 log10 PFU/mL at any day after vaccination; Positive RT-PCR more than 14 days after vaccination; Presence of vaccine virus in tissue by culture, RT-PCR or immunohistochemistry.

• Laboratory exclusion of relevant differential diagnosis such as leptospirosis, viral hepatitis and arboviruses.
• Cases not obeying these strict criteria but that could be plausibly YEL-AVD or YEL-AND may be included, if approved by the investigator or co-investigators.

Exclusion Criteria:

• Cases with adverse event after yellow fever vaccine not severe.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic markers	Whole exome sequencing (WES) will be performed in YEL-AVD cases.	Time frame: 5 years

Collaborators and Investigators

• Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
• Collaborators: Rockefeller University

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2017
• Primary Completion (Estimated): June 1, 2023
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: yellow fever vaccine; genetic factors; neurological disease; viscerotropic disease
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Yellow Fever; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: ASCLIN002/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No