The impact of viral vaccines in immunosuppressed and at-risk individuals

Vaccines have saved millions of lives, but for some individuals with a defective immune system the protection may be uncertain. This thesis aims to assess the immune response following viral vaccines in immunocompromised patients and in other groups at-risk. In paper I the immune response to a modified vaccine schedule against hepatitis A, adding an extra vaccine dose, was tested in patients with rheumatoid arthritis (RA) on immunomodulating drugs. Following two doses,88% of RA patients developed seroprotective antibodies against hepatitis A compared to 94% of healthy controls. In paper II 53 cases of Tick borne encephalitis (TBE) vaccine failure were characterized. The majority of cases were seen in men, 81% were 50 years or older and 51% had co-morbidities. Vaccine failure was most common after three or four doses only, but was seen in up to nine doses. Four out of five had a moderate to severe disease. In paper III the immune response to mRNA vaccines was compared in SARS-CoV-2 experienced and naïve health care workers. Experienced individuals had an increased innate immune cell activation, cytokine and chemokine production and changes in innate gene expression following the first vaccine dose as well as a stronger adaptive response with higher antibody titres and B-cell and CD4+ T-cell activity. The differences were less after the second dose, but three doses were required before an equal immune response was observed in naïve and experienced individuals. In paper IV the immune response to SARS-CoV-2 mRNA vaccine was assessed in patients with chronic kidney disease (CKD) stage 4 and 5 prior to renal replacement therapy. CKD patients were found to have an immune response comparable with healthy controls, with the exception of lower secreted anti-spike antibodies in the saliva and a decreased cytotoxic CD8+ T-cell activity. In conclusion, a deeper understanding of the immune response to vaccines is needed to be able to adapt recommendations and improve outcome in vulnerable group