A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin-based adjuvants.
In the development of mucosal vaccines, cholera toxin (CT) has been shown to be an effective adjuvant and to induce both mucosal and systemic immune responses via a Th2 cell-dependent pathway. However, a major concern for use of mucosal adjuvants such as CT is that this molecule is not suitable for use in humans because of its innate toxicity. Recent vaccine development efforts have emphasized nasal application of antigen and CT for the induction of mucosal IgA responses. When we examined potential toxicity of CT for the central nervous system (CNS), both CT and CT-B accumulated in the olfactory nerves/epithelium and olfactory bulbs of mice when given by the nasal route. The development of effective mucosal vaccines for the elderly is also an important issue; however, only limited information is available. When mucosal adjuvanticity of CT was evaluated in aged mice, an early immune dysregulation was evident in the mucosal immune system. The present review discusses these potential problems for effective mucosal vaccine development.
Fujihashi
Kohtaro
K
Department of Microbiology, BBRB Room 716, Immunobiology Vaccine Center, University of Alabama at Birmingham, Medical Center, 35294-2170, USA. kohtarof@uab.edu
Koga
Toshiya
T
van Ginkel
Frederik W
FW
Hagiwara
Yukari
Y
McGhee
Jerry R
JR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000281:Administration, Intranasal; D000375:Aging / Q000276:immunology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D002648:Child; D002772:Cholera Toxin; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D051379:Mice; D014612:Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D014612:Vaccines; D002772:Cholera Toxin