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 | 2
Appendix to chapter 3 and 4 RICH-2 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Unpublished supplemental data
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Background
The original study protocol included a cross-over design with an influenza re-vaccination at week 4. The reason for this re-vaccination was to minimize the risk of underprotection in immunocompromised patients, who received a reduced dose vaccination. The reason to re-vaccinate already at week 4 was mostly practical: in the RICH-1 study the number of patients lost to follow up increased with every time point, further more we aimed to achieve maximal protection in time for the influenza season.
Wheal size, side effects and immune response
As a quality control wheal size was measured after every intradermal vaccination (Figure 1a). A wheal size of greater than or equal to 6 mm was considered adequate. This was achieved in all but 3 subjects (Figure 1b). The final analysis was done on a intention-to- treat base, however excluding these three subjects from the analysis did not alter outcomes.
Unfortunately, we did not systematically ask subjects to measure the size of the postvac- cination skin rash. Especially in healthy controls, a local reaction of more than 5 cm in diameter was frequently noticed (Figure 1c). As noted in the article, frequency and
%
Figure 1a. Typical wheel (diameter 8 mm) after intradermal vaccination in a HIV-infected patient with lipo-atrophy. 1b. Histogram of wheel size in all subjects. 1c. Painless local skin reaction (maximum diameter 55 mm) in a healthy control 48 hours after intradermal vaccination.
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74 Appendix 2
severity of the local skin reaction was related both to the severity of the immunodeficiency and the subsequent antibody response.
Longterm follow up
At four weeks subjects randomized to the intradermal vaccination (id) arm received a regular intramuscular (im) vaccination and subjects randomized to the im arm received a reduced dose id vaccination. Antibodies were measured at week 0, 4, 8 and 26 (for a subgroup) as presented in Figure 2. In the original publication only the week 4 data are represented graphically for reasons of clarity.
The HIV-groups were the only groups that met the predefined size from the power calcula- tions (90% power to detect a 50% difference in post vaccination GMT in the id versus the im group); the other study groups are used as reference groups.
Revaccination at week 4 did not give a true booster response. Titers did increase in all study groups (except for the rituximab treated patients), but the effect on the protection rate was modest or even absent.
Anti-influenza titers remained stable six months after repeated vaccination in healthy controls but not in HIV-infected individuals. This information is relevant in case of ‘late’
influenza epidemics (as occurred in The Netherlands 2006 and 2007) and in case of cross- equator travel, in which cases HIV-infected individuals might be unprotected. Protection rates, 6 months after repeated vaccination, were as low as 67, 48 and 29% for influenza A/H3N2, A/H1N1 and B, respectively (vs. 100, 71 and 86% in healthy controls; pooled data from im and id vaccination). Protection might even be more short lived in subjects who received only a single vaccine dose.
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Figure 2. Geometric mean titers (95% confidence interval) against influenza A/H3N2, A/H1N1 and influenza B at the different time points.
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