Nasal and Vaginal Vaccinations Have Differential Effects on Antibody Responses in Vaginal and Cervical Secretions in Humans

Johansson, Eva-Liz; Wassén, Lotta; Holmgren, Jan; Jertborn, Marianne; Rudin, Anna

doi:10.1128/iai.69.12.7481-7486.2001

Cited by 160 publications

(115 citation statements)

References 31 publications

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“…Although IgA plasma cells generated in small intestine and colon preferentially home into small intestine and colon, respectively (32), those generated by immunization via nasal cavity preferentially home into nasopharyngeal and respiratory mucosal tissues, but not into intestinal tissues (33,34). Such differential migratory properties of IgA plasma cells in accordance with their tissue origin are likely to be explained in part by their expression of a different set of chemokine receptors (5).…”

Section: Discussionmentioning

confidence: 99%

CC Chemokine Ligands 25 and 28 Play Essential Roles in Intestinal Extravasation of IgA Antibody-Secreting Cells

Hieshima¹,

Kawasaki²,

Hanamoto

et al. 2004

The Journal of Immunology

186

183

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CCL25 (also known as thymus-expressed chemokine) and CCL28 (also known as mucosae-associated epithelial chemokine) play important roles in mucosal immunity by recruiting IgA Ab-secreting cells (ASCs) into mucosal lamina propria. However, their exact roles in vivo still remain to be defined. In this study, we first demonstrated in mice that IgA ASCs in small intestine expressed CCR9, CCR10, and CXCR4 on the cell surface and migrated to their respective ligands CCL25, CCL28, and CXCL12 (also known as stromal cell-derived factor 1), whereas IgA ASCs in colon mainly expressed CCR10 and CXCR4 and migrated to CCL28 and CXCL12. Reciprocally, the epithelial cells of small intestine were immunologically positive for CCL25 and CCL28, whereas those of colon were positive for CCL28 and CXCL12. Furthermore, the venular endothelial cells in small intestine were positive for CCL25 and CCL28, whereas those in colon were positive for CCL28, suggesting their direct roles in extravasation of IgA ASCs. Consistently, in mice orally immunized with cholera toxin (CT), anti-CCL25 suppressed homing of CT-specific IgA ASCs into small intestine, whereas anti-CCL28 suppressed homing of CT-specific IgA ASCs into both small intestine and colon. Reciprocally, CT-specific ASCs and IgA titers in the blood were increased in mice treated with anti-CCL25 or anti-CCL28. Anti-CXCL12 had no such effects. Finally, both CCL25 and CCL28 were capable of enhancing α4 integrin-dependent adhesion of IgA ASCs to mucosal addressin cell adhesion molecule-1 and VCAM-1. Collectively, CCL25 and CCL28 play essential roles in intestinal homing of IgA ASCs primarily by mediating their extravasation into intestinal lamina propria.

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Section: Discussionmentioning

confidence: 99%

CC Chemokine Ligands 25 and 28 Play Essential Roles in Intestinal Extravasation of IgA Antibody-Secreting Cells

Hieshima¹,

Kawasaki²,

Hanamoto

et al. 2004

The Journal of Immunology

186

183

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“…However, it was noted that women in the V imm group developed local Ab responses that differed tremendously in magnitude (8), possibly because vaccine was administered at alternating follicular and luteal phases of the menstrual cycle. It has been reported that biweekly V imm of women on days 10 and 24 of the menstrual cycle is better than random biweekly V imm for induction of specific IgA Ab in cervical secretions (9). However, comparative studies addressing the outcome of V imm in relation to the specific menstrual cycle phases during which Ag is administered have not been performed in humans.…”

mentioning

confidence: 99%

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

Kozlowski

Williams²,

Lynch³

et al. 2002

The Journal of Immunology

205

186

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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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“…However, those immunized vaginally on days 10 and 24 of their menstrual cycle had the greatest amounts of IgG and IgA in cervical secretions, compared to those immunized vaginally irrespective of cycle stage. 115 With these factors in mind, any vaccine targeted to the female reproductive tract must induce a strong CMI and humoral response that is able to overcome the effects of hormonal fluctuations.…”

Section: Problems With Vaccine Developmentmentioning

confidence: 99%

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

Carey

Beagley

2010

American J Rep Immunol

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Citation Carey AJ, Beagley KW. Chlamydia trachomatis, a hidden epidemic: effects on the female reproduction and options for treatment. Am J Reprod Immunol 2010The number of genital tract Chlamydia trachomatis infections is steadily increasing worldwide, with approximately 50–70% of infections asymptomatic. There is currently no uniform screening practice, current antibiotic treatment has failed to prevent the increased incidence, and there is no vaccine available. We examined studies on the epidemiology of C. trachomatis infections, the effects infections have on the female reproductive tract and subsequent reproductive health and what measures are being taken to reduce these problems. Undetected or multiple infections in women can lead to the development of severe reproductive sequelae, including pelvic inflammatory disease and tubal infertility. There are two possible paradigms of chlamydial pathogenesis, the cellular and immunological paradigms. While many vaccine candidates are being extensively tested in animal models, they are still years from clinical trials. With no vaccine available and antibiotic treatment unable to halt the increased incidence, infection rates will continue to increase and cause a significant burden on health care systems.

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Nasal and Vaginal Vaccinations Have Differential Effects on Antibody Responses in Vaginal and Cervical Secretions in Humans

Cited by 160 publications

References 31 publications

CC Chemokine Ligands 25 and 28 Play Essential Roles in Intestinal Extravasation of IgA Antibody-Secreting Cells

CC Chemokine Ligands 25 and 28 Play Essential Roles in Intestinal Extravasation of IgA Antibody-Secreting Cells

Differential Induction of Mucosal and Systemic Antibody Responses in Women After Nasal, Rectal, or Vaginal Immunization: Influence of the Menstrual Cycle

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

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