Antibodies and Antibody-Secreting Cells in the Female Genital Tract after Vaginal or Intranasal Immunization with Cholera Toxin B Subunit or Conjugates

ABSTRACT We studied the antibody response including antibody-secreting cells (ASC) in the female genital tract of mice after mucosal immunizations with the recombinant B subunit of cholera toxin (rCTB) perorally, intraperitoneally, vaginally, and intranasally (i.n.). The strongest genital antibody responses as measured with a novel perfusion-extraction method were induced after vaginal and i.n. immunizations, and these routes also gave rise to specific immunoglobulin A (IgA) and IgG ASC in the genital mucosa. Specific ASC in the iliac lymph nodes, which drain the female genital tract, were seen only after vaginal immunization. Progesterone treatment increased the ASC response in the genital tissue after all mucosal immunizations but most markedly after vaginal immunization. We also tested rCTB as a carrier for human gamma globulin (HGG) and the effect of adding cholera toxin (CT) as an adjuvant for the induction of systemic and genital antibody responses to HGG after vaginal and i.n. immunizations. Vaginal immunizations with HGG conjugated to rCTB resulted in high levels of genital anti-HGG antibodies whether or not CT was added, while after i.n. immunization the strongest antibody response was seen with the conjugate together with CT. In summary, vaginal and i.n. immunization give rise to a specific mucosal immune response including ASC in the genital tissue, and vaginal immunization also elicits ASC in the iliac lymph nodes. We have also shown that rCTB can act as an efficient carrier for a conjugated antigen for induction of a specific antibody response in the genital tract of mice after vaginal or i.n. immunization.

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Generation of Female Genital Tract Antibody Responses by Local or Central (Common) Mucosal Immunization

Infection and Immunity ◽

10.1128/iai.68.10.5539-5545.2000 ◽

2000 ◽

Vol 68 (10) ◽

pp. 5539-5545 ◽

Cited By ~ 51

Author(s):

Hong-Yin Wu ◽

Samira Abdu ◽

Dana Stinson ◽

Michael W. Russell

Keyword(s):

Genital Tract ◽

Molecular Form ◽

Female Genital Tract ◽

Immunoglobulin A ◽

Antibody Responses ◽

Igg Antibody ◽

B Subunit ◽

Iga Antibody ◽

The Common ◽

Female Genital

ABSTRACT Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin. Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses. Although i.vag. immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated. In contrast, i.n. immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva. Moreover, mucosal and systemic antibodies induced by i.n. immunization persisted for at least 12 months. Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.

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Local and Systemic Immune Responses to Rectal Administration of Recombinant Cholera Toxin B Subunit in Humans

Infection and Immunity ◽

10.1128/iai.69.6.4125-4128.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 4125-4128 ◽

Cited By ~ 49

Author(s):

Marianne Jertborn ◽

Inger Nordström ◽

Anders Kilander ◽

Cecil Czerkinsky ◽

Jan Holmgren

Keyword(s):

Immune Responses ◽

Cholera Toxin ◽

Immunoglobulin A ◽

Rectal Administration ◽

Antibody Responses ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit ◽

Antibody Secreting Cells

ABSTRACT The induction of immune responses to rectally administered recombinant cholera toxin B subunit (CTB) in humans was studied. Three immunizations induced high levels of CTB-specific antibody-secreting cells, particular of the immunoglobulin A isotype, in both rectum and peripheral blood. Antitoxin antibody responses in rectal secretions and serum were also found.

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Kinetics of Local and Systemic Immune Responses after Vaginal Immunization with Recombinant Cholera Toxin B Subunit in Humans

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.3.447-452.2005 ◽

2005 ◽

Vol 12 (3) ◽

pp. 447-452 ◽

Cited By ~ 8

Author(s):

Lotta Wassen ◽

Marianne Jertborn

Keyword(s):

Immune Responses ◽

Cholera Toxin ◽

Female Genital Tract ◽

Antibody Responses ◽

Cholera Toxin B Subunit ◽

Igg Antibody ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit ◽

Kinetics Of

ABSTRACT Vaginal vaccination seems to be the best strategy for inducing specific immunoglobulin A (IgA) and IgG antibody responses in the female genital tract. The relative efficiencies of one, two, and three vaginal doses of recombinant cholera toxin B subunit (CTB) in generating mucosal and systemic immune responses in healthy women were evaluated, and the kinetics of the immune responses were monitored for responding volunteers for up to 12 months after the last vaccination. A single dose of CTB failed to generate CTB-specific IgA antibody responses in cervical secretions. Two vaccinations induced significant increases in IgA antitoxin titers in seven of nine volunteers, and four volunteers also developed IgG antitoxin responses. The magnitudes of the responses were 20-fold for IgA antitoxin and 7.1-fold for IgG antitoxin. A third vaccination did not significantly increase the antitoxin responses, although the frequency of IgG responses was slightly higher than that after the second vaccination. In serum, CTB-specific antibodies were observed already after a single vaccination. However, two vaccinations were required to induce marked IgA as well as IgG antitoxin titer increases in the majority of volunteers. The postvaccination levels of antitoxin antibodies in serum were comparable after two and three vaccinations. At 12 months after vaccination, significantly elevated IgA and IgG antitoxin levels in cervical secretions could still be detected in approximately half of the volunteers who had initially responded to the vaccine. Antitoxin titer increases in serum were found in most of the vaccinees at follow-up.

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