TY - JOUR
T1 - Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization
T2 - Influence of the menstrual cycle
AU - Kozlowski, Pamela A.
AU - Williams, Selvi B.
AU - Lynch, Rebecca M.
AU - Flanigan, Timothy P.
AU - Patterson, Rosalyn R.
AU - Cu-Uvin, Susan
AU - Neutra, Marian R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - 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 (Rimm) route, nasal immunization (Nimm) route, or vaginal immunization route during either the follicular (V-FPimm) or luteal (V-LPimm) menstrual cycle phase. Nimm 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 Rimm or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. Nimm induced greatest levels of CTB-specific IgG in sera. Rimm failed to generate CTB-specific IgA in genital tract secretions. Nimm, V-FPimm, and V-LPimm all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FPimm induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FPimm, but not V-LPimm, also induced CTB-specific IgA in rectal secretions. Nimm was superior to V-FPimm 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 Rimm women. These data suggest that in women, Nimm 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-FPimm or Rimm will likely require administration of comparably high nasal vaccine dosages.
AB - 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 (Rimm) route, nasal immunization (Nimm) route, or vaginal immunization route during either the follicular (V-FPimm) or luteal (V-LPimm) menstrual cycle phase. Nimm 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 Rimm or vaginal immunization. Concentrations of Ab induced in sera and secretions were measured by ELISA. None of these routes produced durable salivary Ab responses. Nimm induced greatest levels of CTB-specific IgG in sera. Rimm failed to generate CTB-specific IgA in genital tract secretions. Nimm, V-FPimm, and V-LPimm all produced cervical CTB-specific IgA responses comparable in magnitude and frequency. However, only V-FPimm induced cervical IgA2-restricted Ab to the bacterial LPS vaccine component. V-FPimm, but not V-LPimm, also induced CTB-specific IgA in rectal secretions. Nimm was superior to V-FPimm 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 Rimm women. These data suggest that in women, Nimm 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-FPimm or Rimm will likely require administration of comparably high nasal vaccine dosages.
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U2 - 10.4049/jimmunol.169.1.566
DO - 10.4049/jimmunol.169.1.566
M3 - Article
C2 - 12077289
AN - SCOPUS:0036644724
SN - 0022-1767
VL - 169
SP - 566
EP - 574
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -