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

Abstract

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.

CD4+ T‐cell immunity in the female genital tract is critically dependent on local mucosal immunization

“…immunizations would be a preferentially stronger route than other routes for stimulating genital tract immunity is poorly understood. Nasal immunization may be an effective way to circumvent hormonal influences on genital tract immunity, as it can stimulate high Agspecific IgA levels in the vagina in both irrespective of the hormonal cycle [27]. The ability to use remote-site immunization, such as the nasal mucosa for generation of genital tract immune responses, is based upon the notion of a common mucosal immune system, whereby DCs imprint homing instructions on T and B cells to migrate to remote mucosal membranes, including the genital tract (reviewed [28]).…”

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

“…Similarly, estradiol pretreatment can protect female rhesus macaques from SIV transmission (Smith et al 2000). Interestingly, vaccination studies in humans indicated that vaginal immunizations might be more effective for induction of genital tract antibodies if performed during the midfollicular phase of the menstrual cycle (Kozlowski et al 2002). Whether ovarian steroids directly or indirectly (by acting on innate immune cells) influence Tand B-cell function is an area of active investigation.…”

Control of Simian/Human Immunodeficiency Virus Viremia and Disease Progression after IL-2-Augmented DNA-Modified Vaccinia Virus Ankara Nasal Vaccination in Nonhuman Primates

“…Of all the mucosal routes tested in human and nonhuman primates, only vaccination via the nasal route has stimulated disseminated humoral and cellular mucosal responses (6 -8). For instance, nasal immunization provides better vaginal responses than rectal immunization and can elicit rectal responses as well (8,9). When compared with other mucosal routes, nasal vaccination has also been found to introduce greater systemic Ab responses.…”

“…When compared with other mucosal routes, nasal vaccination has also been found to introduce greater systemic Ab responses. Thus, if immunity is desired at both mucosal and systemic sites, vaccination via the nasal route may be better than other mucosal routes (8).…”