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

2000 ◽  
Vol 68 (10) ◽  
pp. 5539-5545 ◽  
Author(s):  
Hong-Yin Wu ◽  
Samira Abdu ◽  
Dana Stinson ◽  
Michael W. Russell

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.

1998 ◽  
Vol 66 (2) ◽  
pp. 514-520 ◽  
Author(s):  
Eva-Liz Johansson ◽  
Carola Rask ◽  
Margareta Fredriksson ◽  
Kristina Eriksson ◽  
Cecil Czerkinsky ◽  
...  

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.


2004 ◽  
Vol 11 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Marli S. P. Azevedo ◽  
Lijuan Yuan ◽  
Cristiana Iosef ◽  
Kyeong-Ok Chang ◽  
Yunjeong Kim ◽  
...  

ABSTRACT A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05) intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers postchallenge compared to those in the other groups. Statistical analyses of the correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers and protection demonstrated that each of these was an indicator of protective immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA and not IgM or IgG antibody titers in serum were highly correlated (R 2 = 0.89; P < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines among all the vaccinated groups, indicating that the IgA antibody titer is probably the most reliable indicator of protection.


2005 ◽  
Vol 12 (3) ◽  
pp. 447-452 ◽  
Author(s):  
Lotta Wassen ◽  
Marianne Jertborn

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.


1998 ◽  
Vol 66 (8) ◽  
pp. 3995-3999 ◽  
Author(s):  
Jan Kilhamn ◽  
Hans Brevinge ◽  
Ann-Mari Svennerholm ◽  
Marianne Jertborn

ABSTRACT The capacity of an oral inactivated B-subunit–whole-cell cholera vaccine to induce immune responses in patients colectomized due to ulcerative colitis was studied. Two doses of vaccine induced significant mucosal immunoglobulin A (IgA) antibody responses in ileostomy fluid against cholera toxin in 14 of 15 (93%) patients and against whole vibrios in 9 of 15 (60%) cases. The serological responses were lower (but not significantly) than those observed in healthy Swedish volunteers. Increased IgA antitoxin levels were found in ileostomy fluid as late as 2 years after vaccination.


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