Live Enterovirus Vaccine and Type 1 Diabetes

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.

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 poliovaccination 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.

The control group received inactivated poliovirus vaccine (IPV) at the age of 6 and 12 months according to the national immunization protocol in Finland at that time.

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

Serial Oral Polio Vaccine (OPV) was given to intervention group instead of inactivated poliovirus vaccine (IPV).

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

Children's Hospital, University of Helsinki, and Helsinki University Central Hospital and Tampere University Hospital, Finland

Viskari H, Oikarinen S, Hoppu S, Vuorinen T, Huhtala H, Toppari J, Veijola R, Ilonen J, Knip M, Hyoty H. Live attenuated enterovirus vaccine (OPV) is not associated with islet autoimmunity in children with genetic susceptibility to type 1 diabetes: prospective cohort study. Diabetologia. 2018 Jan;61(1):203-209. doi: 10.1007/s00125-017-4410-4. Epub 2017 Sep 2.