Enterovirus Infection, Prediabetic State, Type 1 Diabetes
Conditions
Keywords
Oral polio vaccine, Inactivated polio vaccine, Enterovirus, Type 1 diabetes, Autoantibody
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.
Interventions
BIOLOGICALOral Polio Vaccine (OPV)
Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV).
Sponsors
Tampere University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 2 Months
Healthy volunteers
Yes
Inclusion criteria
* The infants parents give signed consent to participate and their HLA genotype is eligible
Exclusion criteria
* The newborn has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inactivated Polio Vaccine (IPV) The control group received inactivated poliovirus vaccine (IPV) at the age of 6, 12 months and 2, 6 and 9-12 years according to the national immunization protocol in Finland at that time. | 251 |
| 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. After the age of 12 months they were recommend to continue according to the national immunisation programme with IPV at the age of 2, 6 and 9-12 years.
Oral Polio Vaccine (OPV): Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV). | 64 |
| Total | 315 |
Baseline characteristics
| Characteristic | Oral Polio Vaccine (OPV) | Total | Inactivated Polio Vaccine (IPV) |
|---|---|---|---|
| Age, Categorical <=18 years | 64 Participants | 315 Participants | 251 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Finland | 64 participants | 315 participants | 251 participants |
| Sex: Female, Male Female | 30 Participants | 158 Participants | 128 Participants |
| Sex: Female, Male Male | 34 Participants | 157 Participants | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 251 | 0 / 64 |
| other Total, other adverse events | 0 / 251 | 0 / 64 |
| serious Total, serious adverse events | 0 / 251 | 0 / 64 |
Outcome results
Primary
Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum
Appearance of multiple type 1 diabetes associated auto-antibodies (2-4 of the measured four auto-antibodies ICA, IAA, GADA, IA-2A)
Time frame: Through study completion, an average of 11 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Inactivated Polio Vaccine (IPV) | Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum | 17 Participants |
| Oral Polio Vaccine (OPV) | Number of Participants With the Appearance of Type 1 Diabetes Associated Auto-antibodies in Serum | 2 Participants |
Secondary
Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months
Percentage of enterovirus RNA positive stool samples during the follow-up of 24 months in IPV and OPV vaccinated children
Time frame: Up to 24 months of age
Population: Overall 1488 stools samples were collected and analysed from 3 to 24 months in both IPV and OPV groups
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Inactivated Polio Vaccine (IPV) | Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months | 89 stool samples |
| Oral Polio Vaccine (OPV) | Number of Enterovirus RNA Positive Stool Samples During the Follow-up of 24 Months | 221 stool samples |