Modulation of influenza-specific humoral recall responses by CD154 blockade and cyclosporine A (145.28)

Abstract

Abstract Background: Current methods of immunosuppression are broadly inhibitory and thus associated with an increased risk of opportunistic infections. Here we compare the effect of CD154 blockade (αCD154) and Cyclosporine A (CsA) therapy on secondary responses to influenza, when the first immunization was performed before therapy, as might be done in transplant wait-listed patients. Methods. Sixteen cynomologus monkeys were immunized with influenza vaccine in absence of immunosupression and administered a secondary boost immunization with either αCD154 mAb (IDEC-131), CsA, or no treatment. Ab responses against three influenza antigens (H1N1, H3N2, B) were measured by ELISA. An average fold increase >1.4 was considered positive. Results. 14 of 16 animals responded to the primary immunization (I) performed in absence of therapy. In untreated controls, 4/5 animals mounted a strong secondary response (II). With αCD154, 4/6 animals showed mild to strong IgM and IgG, and 2/6 demonstrated either IgM or IgG responses. In contrast, in CsA-treated animals, only 2/5 produced IgM without IgG, and 3/5 mounted low titers of IgG but no IgM. Conclusions. Relative to CsA, αCD154 only moderately suppressed secondary Ab responses to flu antigens. This suggests that αCD154 treatment spares important facets of adaptive immunity against opportunistic infections, potentially conferring a clinically significant advantage over conventional immunosuppression with respect to common pathogens