1. ¹Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA
2. ²Department of Pediatrics, University of Washington, Seattle, Washington, USA
3. ³Allied Research International, Toronto, Ontario, Canada
4. ⁴Genentech Inc., South San Francisco, California, USA

Correspondence: Dr James G. Krueger, The Rockefeller University, 1230 York Ave, NY 10065, New York, USA. E-mail: jgk@rockefeller.edu; Dr Wolfgang Dummer, Genentech Inc., 1 DNA Way, S. San Francisco, CA 94107, USA. E-mail: wdummer@gene.com

Received 6 June 2007; Revised 23 January 2008; Accepted 27 January 2008; Published online 22 May 2008.

Abstract

Efalizumab is a humanized monoclonal CD11a antibody approved for treatment of psoriasis. Its immunomodulatory effects led us study how immune responses are modified and the possible consequences for vaccinations in clinical practice. This was a randomized, single-blind, placebo-controlled, parallel-group study of 12 weeks of subcutaneous efalizumab treatment of patients with moderate psoriasis. Bacteriophage X174 was used as a model neoantigen to assess T-cell-dependent humoral immunity. Tetanus booster vaccine, pneumococcal vaccine, and intracutaneous skin tests were administered to further evaluate humoral and cellular immune responses. During efalizumab treatment, both primary and secondary antibody responses to X174, including IgM/IgG isotype switch, were reduced. There appeared to be naïve T-cell anergy to a neoantigen (X174) during active CD11a blockade, without tolerance to the antigen after efalizumab withdrawal. Secondary humoral immune responses to tetanus booster during treatment were reduced, but antibody titer increases led to protective levels. Responses to pneumococcal vaccination 6 weeks after withdrawal from efalizumab were not affected. Cellular immune responses to intracutaneous recall antigens were reduced during treatment and returned to pretreatment conditions after withdrawal. These results expand our knowledge of how immune responses are modulated in humans by CD11a blockade and have implications for vaccinations of patients treated with this agent.