title: Effect of therapeutic integrin (CD11a) blockade with efalizumab on immune responses to model antigens in humans: results of a randomized, single blind study.
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 phiX174 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 phiX174, including IgM/IgG isotype switch, were reduced. There appeared to be naïve T-cell anergy to a neoantigen (phiX174) 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.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA. Electronic address: jgk@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.affiliation: Allied Research International, Toronto, Ontario, Canada.
authors.forename: Piyush
authors.initials: P
authors.lastname: Patel
authors.affiliation: Genentech Inc., South San Francisco, California, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Gilkerson
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, New York, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: Genentech Inc., South San Francisco, California, USA. Electronic address: wdummer@gene.com.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dummer
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000942:Antigens, Bacterial / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010584:Bacteriophage phi X 174 / Q000276:immunology; D040881:CD11a Antigen / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000494:pharmacology*; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016037:Single-Blind Method; D012882:Skin Tests; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013745:Tetanus Toxoid / Q000494:pharmacology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000942:Antigens, Bacterial; D040881:CD11a Antigen; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines; D013745:Tetanus Toxoid; C472181:efalizumab