Improved Immune Response to Pneumococcal Vaccine in ANCA-Associated Vasculitis

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Investigators find that the proportion of multifunctional CD4 T-cells was found to correlate with the immune response to pneumococcal vaccination.
Investigators find that the proportion of multifunctional CD4 T-cells was found to correlate with the immune response to pneumococcal vaccination.

Suppressing cytomegalovirus (CMV) may improve the immune response to a T cell-dependent pneumococcal vaccination in patients diagnosed with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, according to research published in the Journal of Infectious Diseases.

Expansion of CD4+CD28null T-cells is associated with increased risk for infection, which is the leading cause of death in ANCA-associated vasculitis. This expansion is only present in CMV-seropositive individuals, and investigators hypothesize that subclinical CMV reactivation drives the expansion, thus antiviral therapy may be of benefit to patients.

An open-label clinical trial (ClinicalTrail.gov, NCT01633476) randomly assigned 38 patients with CMV-seropositive ANCA-associated vasculitis to receive either, valaciclovir or no treatment. Virus reactivation was measured monthly in virus and urine and CD4+CD2-8null T cells were enumerated at baseline and at 6 months. Thirty-six patients were vaccinated with a 13-valent pneumococcal vaccine after 6 months, and investigators calculated the antibody-response ratio by assaying serotype-specific IgGbefore and 4 weeks after vaccination.

Valaciclovir treatment suppressed subclinical viral reactivation and reduced the CD4+CD28null T-cell proportion. Improved vaccine response was also correlated with CD4+CD28null T-cell reduction whereas reduced response was associated with CMV reactivation. CD4+CD28null T-cell expansion was also associated with a reduction in the functional capacity of the CD4 compartment.

Investigators did not achieve the target enrollment of 50 patients and found a nonsignificant difference in baseline CD4+CD28null T-cell percentage between the 2 groups. This required paired ratio t-test analysis of change in CD4+CD28null T-cells and examination of differences in the ratios of paired values rather than absolute differences.

The results "support a mechanism whereby CMV infection reduces the immune response to heterologous antigens in patients with ANCA-associated vasculitis" and "provide proof-of-principle for the potential benefit of CMV suppression in ANCA-associated vasculitis." Larger studies will be required to determine the frequency of subclinical CMV reactivation during the acute disease phases and investigate the potential for CMV suppression to aid responses to vaccinations and infection risk reduction.

Reference

Chanouzas D, Sagmeister M, Faustini S, et al. Subclinical reactivation of cytomegalovirus drives CD4+CD28null T-cell expansion and impaired immune response to pneumococcal vaccination in ANCA-associated vasculitis [published online August 9, 2018]. J Infect Dis. doi: 10.1093/infdis/jiy493

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