The common mucosal immune system: from basic principles to enteric vaccines with relevance for the female reproductive tract.
The realization that induction of immune responses at mucosal surfaces may prevent colonization, invasion or dissemination of pathogenic microorganisms has spurred intensive efforts to develop vaccines which elicit effective mucosal immunity. In this paper, recent results are discussed for mice given cholera toxin as both an immunogen and as an adjuvant for inducing both humoral and gastrointestinal mucosal immune responses. Oral administration of cholera toxin alone or with a co-administered protein vaccine tetanus toxoid induces a strong T helper type 2 (TH2) cell response in both Peyer's patches and spleen. Both serum IgG and secretory IgA antibodies specific for cholera toxin or for the co-administered protein tetanus toxoid were induced. When administered parentally, however, no mucosal antibody responses were evident and a mixed TH1- and TH2-type CD4+ T cell response was noted in the spleen. Various vectors are being employed in an effort not only to induce mucosal immune responses but also to direct the response to a TH1-type response, thought to promote strong cell-mediated immune responses, or to a TH2-type response for maximum B cell antibody responses. The ability to manipulate the TH cell responses may provide a more rational approach for the design of vaccines. Although lymphoid tissues of the female reproductive tract differ from that of the gut, many of the strategies and evolving principles may be directly applicable to the development of vaccines designed to prevent sexually transmitted diseases.
Department of Microbiology, UAB Medical Center, Birmingham, Alabama 35294.
J R
JR
McGhee
J
J
Xu-Amano
C J
CJ
Miller
R J
RJ
Jackson
K
K
Fujihashi
H F
HF
Staats
H
H
Kiyono
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D010581:Peyer's Patches / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D000906:Antibodies; D022121:Cholera Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D013745:Tetanus Toxoid