Immunizations in immunocompromised hosts : effects of immune modulating drugs and HIV on the humoral
immune response
Gelinck, L.B.S.
Citation
Gelinck, L. B. S. (2010, March 17). Immunizations in immunocompromised hosts : effects of immune modulating drugs and HIV on the humoral immune response. Retrieved from https://hdl.handle.net/1887/15094
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
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Appendix | 1
Appendix to chapter 1 and 2 Immune Response in
Immunocompromised Hosts (RICH)-1 study – additional data
L.B.S. Gelinck
Dept. of Infectious Diseases, Leiden University Medical Center, Leiden and
Dept. of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
Unpublished supplemental data
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Immune Response in Immunocompromised Hosts (RICH)-1 study – additional data
Study scheme
The pneumococcal (chapter 1) and influenza (chapter 2) vaccination (RICH-1) studies were done simultaneously within the same study population. The study scheme is rep- resented in Figure 1: patients received an influenza vaccination at week 0, with a second influenza vaccination at week four, to study if this would increase the number of subjects with a protective titer. At week 4 a pneumococcal vaccination was administered simultane- ously with the influenza vaccination, a final evaluation was done at week 8.
Figure 1. Flowchart with a schematic representation of the RICH-1 study, including the number of participants at the different time points.
The number of patients lost-to-follow up was high in this study, increasing with every study visit. An important reason for this was that anti-TNF was not readily available in 2003. Anti-TNF was used in clinical trials as a rescue treatment for patients failing other drug regimens. Many patients travelled long distance to be included in these treatment trials, the travel associated with the extra visits for the vaccination study proved to be problematic for some of the patients.
Follow up
that completed all three study visits, revaccination did not give rise to a booster response (Figure 2); only a modest increase of patients with a protective titer was seen (Figure 3).
Thus, repeated influenza vaccination with only a four week interval does not provide a relevant increase of anti-influenza The influenza follow-up data are presented in Figure 2 and 3. Within the group of patients immunity.
Evaluation of different immunological pathways
As described in de general discussion of this thesis, evaluating both a T-cell-dependent (influenza) and T-cell-independent (pneumococcal) vaccine, within the same patient cohort gave us the opportunity to study the immunological properties of anti-TNF alone and in combination with other drugs. Table 1 shows correlations between the response on influenza antigens (the protection rate as defined in chapter 2) and the response upon
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46 Appendix 1
pneumococcal antigens (the response rate as defined in chapter 1). The strength of the correlation is coded by the colour of the cells, p-values are coded by asterixes. As would be expected, there are clear correlations among the influenza antigens on one hand and pneumococcal antigens on the other hand. There is, however, a striking absence of correla- tions between the response upon influenza and pneumococcal antigens. Most correlations found were weak (Pearson’s correlation coefficient <0.5), only responses upon the two influenza A strains (H3N2 and H1N1) and the responses upon PPS 19F and two of the other PPSs showed stronger correlations. The fact that the responders upon influenza vac- cination and the responders upon pneumococcal vaccination do not correspond with each other, underscores the fact that different immunological pathways are being evaluated.
Figure 2. Geometric mean titers (95% confidence interval) against influenza A/H3N2, A/H1N1 and influenza B at the different time points.
Figure 3. Protection rates (the percentage of subjects with a titer >40) at week 0 (prevaccination), 4 and 8 for influenza A/H3N2, A/H1N1 and influenza B.
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In conclusion repeated influenza vaccination with only a four week interval does not provide a relevant increase of anti-influenza immunity. Influenza and pneumococcal vac- cination respectively evaluate T-cell-dependent and T-cell-independent pathways.
Table 1. Cross tabulation, indicating positive correlations for responders upon influenza and PPS antigens.
H3 H1 B 6B 9V 19F 23F
A/H3N2 HC **
TNF- * **
TNF+ *
A/H1N1 HC **
TNF- * **
TNF+ *
B HC
TNF- ** **
TNF+
PPS6B HC
TNF- ** *
TNF+
PPS9V HC
TNF- *
TNF+ ** **
PPS19F HC
TNF- ** **
TNF+ ** *
PPS23F HC
TNF- * * **
TNF+ ** *
Pearson’s correlation coefficient: white < 0.3; grey 0.3-0.5; black >0.5
* correlation is significant at 0.05 level (two-tailed); ** significant at 0.01 level (two-tailed)
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