Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children

Abstract

Aims/hypothesis: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix®, was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix® similarly increased the risk of islet autoimmunity or type 1 diabetes.

Methods: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter.

Results: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix®. By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix®. The analyses were adjusted for confounding factors.

Conclusions/interpretation: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes.

Keywords: Influenza vaccine; Islet autoimmunity; Pandemrix; Squalene; Swine flu; Type 1 diabetes; Vaccination.

Fig. 1

Flow chart of the study population

Fig. 2

H1N1 coverage as of 1 March 2010 among children born in Finland and Sweden; coverage shown for children aged < 6 months (solid black bars), 6–11 months (solid white bars), 12–23 months (solid light grey bars), 24–36 months (solid dark grey bars) and ≥ 36 months (light grey striped bars)

Fig. 3

Kaplan–Meier curves showing the cumulative percentage of vaccinated (solid line) and unvaccinated (dashed line) children developing islet autoantibodies (IA) in (a) Finland with an average follow-up time of 5.3 years for vaccinated (n = 976) and 4.7 years for unvaccinated (n = 397) children and (b) Sweden with an average follow-up time of 5.4 years for vaccinated (n = 1309) and 5.0 years for unvaccinated (n = 563) children; multiple islet autoantibodies in (c) Finland with an average follow-up time of 5.3 years for vaccinated (n = 1000) and 4.8 years for unvaccinated (n = 400) children and (d) Sweden with an average follow-up time of 5.5 years for vaccinated (n = 1347) and 5.2 years for unvaccinated (n = 569) children. Type 1 diabetes (T1D) in (e) Finland with an average follow-up time of 5.5 years for vaccinated (n = 1027) and 5.1 years for unvaccinated (n = 410) children and (f) Sweden with an average follow-up time of 5.7 years for vaccinated (n = 1384) and 5.4 years for unvaccinated (n = 578) children, after the child was vaccinated or after 1 October 2009 for the children who were not vaccinated