Outcome of influenza vaccination in combat-related post-traumatic stress disorder (PTSD) patients

Abstract

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after exposure to extreme traumatic experience such as war trauma, and is accompanied by fear, helplessness or horror. Exposure to trauma can result in immune dysregulation and influence susceptibility to infectious disease as well as vaccine efficacy. The aim of the study was to determine the relation of psychological stress and the immune response to influenza vaccination in combat-related PTSD patients (n = 28). Detection of anti-viral antibody titre was performed by inhibition of haemagglutination assay. Ex vivo tetramer staining of CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination. Twenty patients showed a fourfold antibody titre increase to one or both influenza A viral strains, and 18 of them showed the same response for both influenza B viral strains. Ten of 15 healthy controls showed a fourfold rise in antibody titre to both influenza A viral strains and eight of them showed the same response for both influenza B viral strains. HLA-A*0201(+) PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination. Although those PTSD patients had a lower number of influenza-specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination. The generated humoral and cellular immune response in PTSD patients argues against the hypothesis that combat-related PTSD in war veterans might affect protection following influenza vaccination.

Fig. 1

Representative dot plots of haemagglutinin (HA)_344−353 and HA_541−549 tetramer staining. Recently activated (CD38 positive, upper right quadrant) and resting (CD38 negative, lower right quadrant) number of tetramer positive CD3⁺ CD8⁺ cells in peripheral blood in HLA-A*0201⁺ post-traumatic stress disorder (PTSD) patients (a) before and 14 days after vaccination. The x-axis represents staining with tetramers and the y axis represents staining with CD38; (b) a similar type of staining in healthy control subjects.

Fig. 2

Comparison of the number of influenza-specific T cells in immunized individuals. Number of recently activated CD38⁺ T cells specific for A/New Caledonia/H1N1 antigens haemagglutinin (HA)_344−353 (a) and HA_541−549 (b) in 50 000 CD3⁺ CD8+ T cells in HLA*A0201⁺ vaccinated post-traumatic stress disorder (PTSD) patients (filled triangles) and controls (filled circles) before and 14 days after vaccination. Median number of tetramer⁺ CD38⁺ in 50 000 CD8⁺ T cells is represented by black (PTSD patients) and dotted (controls) horizontal bars. The number of antigen-specific T cells before and after vaccination was analysed by Wilcoxon's matched pair test. Comparison of the number of influenza-specific T cells in immunized individuals was performed by Mann–Whitney U-test.