Live Enterovirus Vaccine and Type 1 Diabetes

Phase 1

Completed

• Conditions: Enterovirus Infection; Prediabetic State; Type 1 Diabetes
• Interventions: Biological: Oral Polio Vaccine (OPV)

• Registration Number: NCT02961595
• Lead Sponsor: Tampere University

Brief Summary

Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. This study evaluated whether early serial exposures to three replication-competent enterovirus strains (live poliovirus vaccine, OPV) can influence the immunity to other enteroviruses and the possible initiation of autoantibodies e.g. islet autoimmunity in young genetically predisposed children.

Detailed Description

Enteroviruses have been associated with type 1 diabetes in several studies. Enterovirus infections may either increase or decrease the risk of type 1 diabetes depending on the age of infection and the type of enterovirus in question. There is remarkable homology between the structure of poliovirus and other enteroviruses. It has been shown in previous studies that the T-lymphocytes recognize these structures and cross-react with different enterovirus serotypes. Our hypothesis is that polio vaccination induces a cross-reacting T-cell response which strengthens enterovirus immunity and thus accelerate the elimination of the enterovirus infections. We evaluated whether early serial live enterovirus vaccine (oral polio vaccine, OPV) can influence the enterovirus immunity and initiation of islet autoimmunity in young genetically predisposed children.

This study was carried out in the birth cohort of the ongoing Diabetes Prediction and Prevention (DIPP) study in Finland. All the children carried HLA-DQ genes conferring moderately increased risk for type 1 diabetes (HLA DQB1\*0302/x, x≠ DQB1\*0201, \*0301, \*0602). Sixty-four children (34 males) were given doses of OPV (Polio Sabin®, SB Biologicals, Rixensart, Belgium) at the age of 2, 3, 6 and 12 months during the years 1999-2000 (two drops per os in each dose). This vaccine includes attenuated replication competent strains of the three poliovirus types (polioviruses 1, 2, 3) leading to infection in vaccinated children. The control group comprising 251 children received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time. After the age of 12 months both groups were recommended to continue the national immunization program with IPV vaccine.

All children were followed regularly from birth with blood samples taken at 3-12 months interval for detection of type 1 diabetes-associated autoantibodies in serum including insulin autoantibodies (IAA), islet cell cytoplasmic antibody (ICA), insulinoma-associated protein 2 antibodies (IA-2A) and GAD antibodies (GADA) (5-7). Stool samples were collected monthly at the age of 2-24 months and systematically screened for the presence of enterovirus and using RT-PCR.

Study Timeline

• Study Start: 1999-10
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Study First Submitted: 2016-11-02
• Study First Submitted QC: 2016-11-10
• Study First Posted: 2016-11-11
• Results First Submitted: 2018-06-01
• Results First Submitted QC: 2024-02-01
• Status Verified: 2024-07
• Results First Posted: 2024-07-18
• Last Update Submitted: 2024-07-18
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 315

Inclusion Criteria

• The infants parents give signed consent to participate and their HLA genotype is eligible

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Exclusion Criteria

• The newborn has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral Polio Vaccine (OPV)	Oral Polio Vaccine (OPV)	Intervention group were given doses of oral polio vaccine OPV (Polio Sabin®) at the age of 2, 3, 6 and 12 months.

Primary Outcome Measures

Name	Time	Method
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum	Through study completion, an average of 11 years	Appearance of multiple type 1 diabetes associated auto-antibodies (2-4 of the measured four auto-antibodies ICA, IAA, GADA, IA-2A)

Secondary Outcome Measures

Name	Time	Method
Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months	Up to 24 months of age	Percentage of enterovirus RNA positive stool samples during the follow-up of 24 months in IPV and OPV vaccinated children