Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: influence of the menstrual cycle.
A cholera vaccine containing killed vibrios and cholera toxin B subunit (CTB) was used to compare mucosal immunization routes for induction of systemic and mucosal Ab. Four groups of women were given three monthly immunizations by the rectal immunization (R(imm)) route, nasal immunization (N(imm)) route, or vaginal immunization route during either the follicular (V-FP(imm)) or luteal (V-LP(imm)) menstrual cycle phase. N(imm) was performed with 10-fold less vaccine to determine if administration of less Ag by this route can, as in rodents, produce mucosal Ab responses comparable to those induced by higher dose R(imm) or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. N(imm) induced greatest levels of CTB-specific IgG in sera. R(imm) failed to generate CTB-specific IgA in genital tract secretions. N(imm), V-FP(imm), and V-LP(imm) all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FP(imm) induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FP(imm), but not V-LP(imm), also induced CTB-specific IgA in rectal secretions. N(imm) was superior to V-FP(imm) for producing rectal CTB-specific IgA, but the greatest amounts of CTB-specific IgA and LPS-specific IgA, IgG, and IgM Ab were found in rectal secretions of R(imm) women. These data suggest that in women, N(imm) alone could induce specific Ab in serum, the genital tract, and rectum. However, induction of genital tract and rectal Ab responses of the magnitude generated by local V-FP(imm) or R(imm) will likely require administration of comparably high nasal vaccine dosages.
Kozlowski
Pamela A
PA
GI Cell Biology Research Laboratory, Children's Hospital, and Department of Pediatrics, Harvard University, Boston, MA 02115, USA. pamela.kozlowski@tch.harvard.edu
Williams
Selvi B
SB
Lynch
Rebecca M
RM
Flanigan
Timothy P
TP
Patterson
Rosalyn R
RR
Cu-Uvin
Susan
S
Neutra
Marian R
MR
D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000918:Antibody Specificity; D002584:Cervix Uteri / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005498:Follicular Phase / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008183:Luteal Phase / Q000276:immunology; D008597:Menstrual Cycle / Q000276:immunology*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D012463:Saliva / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism
D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D002772:Cholera Toxin