Genital Tract Immunity Research Articles

Role of route of delivery on Chlamydia abortus vaccine-induced immune responses and genital tract immunity in mice.

We investigated if the efficacy of a Chlamydia abortus (Cab) subunit vaccine is influenced by route of administration. Thus, female CBA/J mice were immunized either by mucosal or systemic routes with Vibrio cholerae ghost (VCG)-based vaccine expressing T and B cell epitopes of Cab polymorphic membrane protein (Pmp) 18D, termed rVCG-Pmp18.3. Vaccine evaluation revealed that all routes of vaccine delivery induced a Th1-type antibody response after a prime boost or three-dose immunization regimen. Also, the intranasal and rectal mucosal and intramuscular systemic routes induced cross-reactive neutralizing antibodies against homologous and heterologous Cab strains. Irrespective of the route of immunization, the vaccine elicited a Th1-type cytokine response (IFN-γ/IL-4 >1) in immunized mice. Analysis of reduction in genital Cab burden as an index of protection showed that immunization induced substantial degrees of protection against infection, irrespective of route of delivery with the intranasal and rectal mucosal routes showing superior levels of protection 12 days postchallenge. Furthermore, there was correlation between the humoral and cellular immune response and protection was associated with the Cab-specific serum IgG antibody avidity and IFN-γ. Thus, while route of administration impacts vaccine efficacy, the rVCG-Pmp18.3-induced protective immunity against Cab respiratory infection can be accomplished by both mucosal and systemic immunization.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1β) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.

Review: Bovine foetal mortality - risk factors, causes, immune responses and immuno-prophylaxis.

This review of bovine foetal mortality (>42d gestation) concluded that while the majority of risk factors associated with sporadic loss operate at animal-level, e.g. foetal plurality, those that operate at herd-level, e.g. some foetopathogenic infections, are more likely to result in abortion outbreaks. While the causes of foetal mortality have traditionally been classified as infectious and non-infectious, in fact, the latter category is a diagnosis of exclusion, generally without determination of the non-infectious cause. This review has also established that the traditional dichotomisation of infectious agents into primary and secondary pathogens is based on a flawed premise and these terms should be discontinued. The delicate balance of the maternal gestational immune system between not rejecting the allograft (conceptus) but rejecting (attacking) foetopathogens is stage-of-pregnancy-dependent thus the timing of infection determines the clinical outcome which may result in persistent infection or foetal mortality. Utilisation of our knowledge of the materno-foetal immune responses to foetopathogenic infection has resulted in the development of numerous mono- and polyvalent vaccines for metaphylactic or prophylactic control of bovine foetal mortality. While some of these have been shown to significantly contribute to reducing the risk of both infection and foetal mortality, others have insufficient, or conflicting evidence, on efficacy. However, recent developments in vaccinology, in particular the development of subunit vaccines and those that stimulate local genital tract immunity, show greater promise.

Sublingual Boosting with a Novel Mucoadhesive Thermogelling Hydrogel Following Parenteral CAF01 Priming as a Strategy Against Chlamydia trachomatis.

Chlamydia trachomatisis the most prevalent sexually transmitted disease of bacterial origin. The high number of asymptomatic cases makes it difficult to stop the transmission, requiring vaccine development. Herein, a strategy is proposed to obtain local genital tract immunity againstC. trachomatisthrough parenteral prime and sublingual boost. Subcutaneous administration of chlamydia CTH522 subunit vaccine loaded in the adjuvant CAF01 is combined with sublingual administration of CTH522 loaded in a novel thermosensitive and mucoadhesive hydrogel. Briefly, a ternary optimized hydrogel (OGEL) with desirable biological and physicochemical properties is obtained using artificial intelligence techniques. This formulation exhibits a high gel strength and a strong mucoadhesive, adhesive and cohesive nature. The thermosensitive properties of the hydrogel facilitate application under the tongue. Meanwhile the fast gelation at body temperature together with rapid antigen release should avoid CTH522 leakage by swallowing and increase the contact with sublingual tissue, thus promoting absorption.In vivostudies demonstrate that parenteral-sublingual prime-boost immunization, using CAF01 and OGEL as CTH522 vaccine carriers, shows a tendency to increase cellular (Th1/Th17) immune responses when compared to mucosal or parenteral vaccination alone. Furthermore, parenteral prime withCAF01/CTH522followed by sublingual boosting with OGEL/CTH522 elicits a local IgA response in the genital tract.

Increased immune cell infiltration contribute to enhanced protective immunity following co-delivery of VCG Chlamydia vaccine with Flt3L

Abstract Chlamydia trachomatis remains the commonest bacterial cause of sexually transmitted infections worldwide and can lead to pelvic inflammatory disease and infertility. Although antibiotics are effective against Chlamydia, most infections are asymptomatic suggesting the use of an effective vaccine may be the best approach for preventing these infections and the associated sequelae. We previously showed rectal (IR) immunization was a viable mucosal route for inducing female genital tract immunity and that the Fms-like tyrosine kinase 3-ligand (Flt3L; FL) enhanced the protective immunity of a Vibrio cholerae ghost (VCG)-based Chlamydia vaccine. However, the mechanism of immune enhancement was not investigated. In this study, we investigated if differences in the type and number of immune cells infiltrating mucosal and systemic tissues of mice could account for the observed immune enhancement following immunization. Mice were immunized IR with rVCG co-expressing the C. trachomatis polymorphic membrane protein D (PmpD) and porin B (PorB) proteins (rVCG-PmpD/PorB) with and without FL. Vaccine evaluation was based on measurement of IFN-γ cytokine, T cell proliferation, protection against intravaginal infection, and the differential profile of immune cells infiltrating mucosal and systemic tissues of mice using flow cytometry. The results showed co-delivery of vaccine with FL significantly enhanced IFN-γ levels and proliferation of splenic CD4+ immune T cells, as well as increased infiltration of immune cells in the spleen and genital tract tissues of mice. The results indicate the increased immune cell infiltration contribute to the enhanced protective immunity following co-delivery of VCG vaccine with FL.

Type I IFN signalling is required for cationic adjuvant formulation (CAF)01-induced cellular immunity and mucosal priming

Despite being in the midst of a global pandemic of infections caused by the pathogen Chlamydia trachomatis, a vaccine capable of inducing protective immunity remains elusive. Given the C. trachomatis mucosal port of entry, a formulation compatible with mucosal administration and capable of eliciting potent genital tract immunity is highly desirable. While subunit vaccines are considered safer and better tolerated, these are typically poorly immunogenic and require co-formulation with immune-potentiating adjuvants. However, of the adjuvants licensed for use in humans, very few drive robust cellular responses, a pre-requisite for protection against C. trachomatis infection. Recently, the cationic adjuvant formulations (CAF) have been shown to induce robust humoral and cellular immunity in pre-clinical models of chlamydia, malaria and tuberculosis (TB). Here, we demonstrate that CAF01 induces potent immune responses when combined with the major outer membrane protein (MOMP) of C. trachomatis following parenteral immunisation and also as part of a heterologous prime/boost regime. We show that a subcutaneous prime with CAF01-adjuvanted recombinant MOMP licenses antigen-specific immunity at distant mucosal sites which can be activated following oral antigen re-encounter in the absence of concomitant adjuvant stimulation. Finally, we shed light on the mechanism(s) through which CAF01 elicits robust antigen-specific immunity to co-formulated MOMP via type I interferon (IFN) signalling.

Isolation of Naturally Released Gonococcal Outer Membrane Vesicles as Vaccine Antigens.

The emergence and spread of fully antimicrobial resistant Neisseria gonorrhoeae (GC) highlights a clear need for next-generation antigonococcal therapeutics. A broadly reactive anti-GC vaccine would best address this global public health threat. Polyantigenic outer membrane vesicles (OMVs) derived from GC can overcome the challenges posed by GC's high rate of phase and antigen variation. In fact, GC OMVs have already shown promise as a vaccine antigen; however, all previous studies have utilized vesicles contaminated by RMP, a bacterioprotective antigen known to entirely abrogate vaccine-induced bactericidal activity in vivo. Additionally, these studies primarily utilized vesicles isolated through techniques like membrane disruption with detergents, which are known to increase contamination of cytoplasmic components as compared to naturally released OMVs (nOMVs). This chapter describes the isolation and characterization of naturally released nOMVs through sequential size and weight restrictive filtration. nOMVs are characterized by morphology, proteomics, and bioactivity via various methods. Herein we also describe methods for further evaluation of the innate and induced immunogenicity of rmp-deficient GC nOMVs by cell stimulation and murine vaccination. Per these methods, nOMVs are found to be largely homogenous spherical structures approximately 70nm in diameter containing a consistent subset of GC outer membrane proteins. The rmp-deficient vesicles demonstrate a morphology and, with the exception of RMP, antigenic profile consistent with that of nOMVs derived from wild time N. gonorrhoeae. Additionally, vesicles lacking RMP are able to engage and strongly activate a diverse array of pattern recognition receptors in vitro. These methods lay the groundwork for future experiments examining the in vivo protective efficacy of the anti-GC response induced by these nOMVs as well as studies examining the mechanism of vaccine induced female genital tract immunity.

The composition of the vaginal microbiome in first trimester pregnant women influences the level of autophagy and stress in vaginal epithelial cells

Epithelial cells lining the vagina are major components of genital tract immunity. The influence of the vaginal microbiome on properties of host epithelial cells is largely unexplored. We evaluated whether differences in the most abundant lactobacilli species or bacterial genera in the vagina of first trimester pregnant women were associated with variations in the extent of stress and autophagy in vaginal epithelial cells. Vaginal swabs from 154 first trimester pregnant women were analyzed for bacterial composition by amplification and sequencing of the V1–V3 region of bacterial 16S rRNA genes. Vaginal epithelial cells were lysed and autophagy quantitated by measurement of p62. Intracellular levels of the inducible 70kDa heat shock protein (hsp70), an indicator of cell stress and an autophagy inhibitor, were determined. When Lactobacillus crispatus was the most abundant member of the vaginal microbiota, epithelial p62 and hsp70 levels were lowest as compared to when other bacterial taxa were most abundant. The highest concentrations of p62 and hsp70 were associated with Streptococcus and Bifidobacterium abundance. The p62 level associated with Gardnerella abundance was lower than that observed when lactobacilli other than L. crispatus were most abundant. In conclusion, in the first trimester of pregnancy the abundance of different bacterial taxa is associated with variations in autophagy and magnitude of the stress response in vaginal epithelial cells.

Immunization with a VCG-based vaccine protects against Chlamydia-induced infertility in the mouse genital infection model

Abstract Chlamydia trachomatis genital infections constitute a major public health challenge due to the significant morbidity that includes pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility. An effective vaccine is required to protect against infection and prevent development of upper genital tract pathology. Previous studies showed intramuscular immunization with a Vibrio cholerae ghost (VCG)-based chlamydial vaccine induced cross protective immunity in mice but its ability to protect against upper genital tract pathology was not evaluated. We sought to assess the ability of rectal immunization with this vaccine to protect against upper genital tract pathology following infection with a heterologous chlamydial serovar in the mouse model. Female mice were rectally immunized with VCG expressing select C. trachomatis serovar D outer membrane proteins and challenged intravaginally with live serovar E chlamydiae 2 weeks postimmunization (PI) to evaluate cross protection. To evaluate upper genital tract pathology, mice received a repeat challenge infection 8 weeks after initial challenge. Rectal immunization elicited high levels of antigen-specific Th1 cell-mediated and humoral immune responses in mucosal and systemic tissues. Furthermore, immunization induced cross-protective immunity that reduced the length and intensity of genital chlamydial shedding and protected against Chlamydia-induced infertility and tubal pathologies. The ability of the VCG vaccine candidate to elicit heterotypic genital tract immunity and protect against Chlamydia-induced upper genital tract pathology is remarkable and highlights its potential for development as a universal chlamydial vaccine candidate.

Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D

Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D

Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus cholera toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity.

Induction of local antiviral immune responses at the mucosal portal surfaces where HIV-1 and other viral pathogens are usually first encountered remains a primary goal for most vaccines against mucosally acquired viral infections. Exploring mucosal immunization regimes in order to find optimal vector combinations and also appropriate mucosal adjuvants in the HIV vaccine development is decisive. In this study we analyzed the interaction of DNA-IL-12 and cholera toxin B subunit (CTB) after their mucosal administration in DNA prime/MVA boost intranasal regimes, defining the cooperation of both adjuvants to enhance immune responses against the HIV-1 Env antigen. Our results demonstrated that nasal mucosal DNA/MVA immunization schemes can be effectively improved by the co-delivery of DNA-IL-12 plus CTB inducing elevated HIV-specific CD8 responses in spleen and more importantly in genital tract and genito-rectal draining lymph nodes. Remarkably, these CTL responses were of superior quality showing higher avidity, polyfunctionality and a broader cytokine profile. After IL-12+CTB co-delivery, the cellular responses induced showed an enhanced breadth recognizing with higher efficiency Env peptides from different subtypes. Even more, an in vivo CTL cytolytic assay demonstrated the higher specific CD8 T-cell performance after the IL-12+CTB immunization showing in an indirect manner its potential protective capacity. Improvements observed were maintained during the memory phase where we found higher proportions of specific central memory and T memory stem-like cells T-cell subpopulations. Together, our data show that DNA-IL-12 plus CTB can be effectively employed acting as mucosal adjuvants during DNA prime/MVA boost intranasal vaccinations, enhancing magnitude and quality of HIV-specific systemic and mucosal immune responses.

Rectal immunization with an rVCG vaccine protects against genital Chlamydia challenge (VAC7P.962)

Abstract Pelvic inflammatory diseases consequent to Chlamydia trachomatis infections is a major public health challenge with frequent asymptomatic infections precluding in early diagnosis and treatment making clinical presentation of sequelae often the first indication of infection. Development of a safe, efficacious and affordable vaccine holds promise for the global spread of Chlamydia genital infections. Previously we have shown that intramuscular(IM) vaccination of Vibrio cholerae ghosts (VCG) expressing Porin B and PmpD showed protection of mice against intravaginal infections via the development of a cellular ( Th1) as well as humoral ( IgG2a and IgA) immunity. The present study was undertaken to examine the potential of rectal immunization for the induction of genital tract immunity against heterologous Chlamydia infection in mice. The impact of immunization with the VCG vaccine in combination with Flt3 Ligand (FL) on induction of immunity was also investigated. The results demonstrate that both IM and IR rVCG immunizations elicited high levels of antigen-specific Th1 cell-mediated and humoral immune responses that were enhanced following co-immunization with FL. Also, rectally immunized mice were significantly protected against heterologous infection with serovar E Chlamydia 2 weeks post immunization. These results highlight the potential of rectal immunization for eliciting immunity in the female genital tract against Chlamydia and other sexually transmitted diseases.

Comparison of normalization methods for measuring immune markers in cervical secretion specimens

Ophthalmic sponges are used to collect undiluted cervical secretions for assessment of markers of genital tract immunity. Heterogeneity in absorbed and extracted sample volumes requires normalization in order to make valid inter-individual comparisons. We evaluated the performance of adjustment by weight and total protein on normalizing inter-individual variability of immune marker measurement due to differences in volume collection. Normalization to total protein resulted in a minimal loss of usable specimens and a significant reduction in the correlation of immune marker concentration to specimen weight compared to weight adjustment. Total protein normalization appeared to be more effective than weight adjustment in reducing the dependence of cervical immune marker concentrations on differences in specimen volume.

Female genital tract immunity: distinct immunological challenges for vaccine development

The population explosion and unintended pregnancies, sexually transmitted diseases including human immunodeficiency virus, and cervical cancer, are major challenges to health worldwide. Their prevention might be achieved through vaccination-based approaches to activate specific immunity against pathogen- or fertility-associated antigens in the female genital tract (FGT). This article aims to review methodologies for enhancing adaptive immunity in the FGT to maximize the response to vaccination. Most components of the adaptive and innate mucosal immune system are present in the FGT and several features are common with the nasopharynx/bronchial and gastrointestinal tracts. In contrast to other mucosal sites, the FGT has minimal local lymphoid tissue. Other sites primarily produce IgA and IgM while in the FGT, especially the vaginocervix, IgG is the predominant immunoglobulin secreted. In rodents, data exist to substantiate a common mucosal immune system interconnecting the nasal/bronchial, gastrointestinal, and female genital tracts. The intranasal route seems the most efficacious to induce an immunity in the FGT especially when combined with a systemic or parenteral route. In humans, for induction of secretory IgA and IgG antibodies in the FGT, immunization by the nasal or the vaginal route is effective. In vaginal immunization, a strong and consistent antibody response is best achieved following vaccination during the follicular phase of the menstrual cycle. Antibodies administered systemically percolate into the FGT and can provide immunoprotection against target molecules or cells. Thus, as well as active immunization using selected routes, the passive immunization approach may provide a viable alternative to vaccinology for future development.

Increases in Human Papillomavirus Detection During Early HIV Infection Among Women in Zimbabwe

Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV). One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes. We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models. These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition.

Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis

Objectives:To compare cervical concentrations of numerous cytokines/chemokines in women with bacterial vaginosis (BV) compared with the levels detected after BV resolution and determine if hormonal contraceptive use modulates the local...

Characteristic of local antichlamydial immunity in infertile women

Objective: to determine the presence of C. trachomatis in upper genital tract and humoral immunity an laparoscopic examination in 202 patients with different infertility factors. Chlamydial persistence in endometrial and tubal tissues was correlated with circulating IgA to C.trachomatis in peritoneal fluid in tubal factor infertility (TFI) (73.5%). IgA may be recommented additional diagnostic factor of chlamydial infection of upper genital tract in TFI.

The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques.

A number of studies have shown that the ovarian hormone cycle affects genital tract immunoglobulin (Ig) levels and T cell function in both humans and rhesus monkeys. We hypothesized that shifts in immune cell populations occurring in response to hormone cycles are involved in the observed changes in genital tract immunity. To test this hypothesis, we characterized the type, number, and distribution of immune cells in the cervicovaginal mucosa at different stages of the menstrual cycle. Tissues from 18 normal female rhesus macaques were studied by immunohistochemistry and computerized morphometric analysis. The number and distribution of CD1a+ Langerhans' cells, CD2+, CD3+, CD4+, and CD8+ T cells, CD20+ B cells, and surface Ig+ plasma cells did not change in samples collected at the different stages of the cycle. However, in no relation to the stage of the menstrual cycle, the number of Langerhans' cells and other immune cell types was different in the various regions of the cervicovaginal mucosa examined. In addition, variation in thickness of the ectocervical and vaginal epithelium during a normal menstrual cycle of rhesus macaques is not accompanied by changes in intraepithelial immune cell populations. We conclude that steroid hormones do not influence genital mucosal immunity by changing the number or distribution of immune cells in the lower reproductive tract.

Changes in mucosal immunity of the adolescent genital tract throughout the menstrual cycle

BACKGROUND: Females may be most susceptible to STDs during menses and the follicular phase of the menstrual cycle. Research in adults has shown that genital tract immunity is most suppressed as unopposed estrogen peaks at ovulation; adolescents may be more responsive to estrogen, resulting in greater local immunosuppression and higher risk of STD. Study objectives were to (1) characterize mucosal immunity of the adolescent genital tract during the cycle and (2) determine if adolescents have more suppressed immunoglobulin (Ig) levels in the follicular phase than adults.METHODS: Girls age 15-17 years were eligible if they were ≥ 2 years post-menarche, had regular cycles, had had sex, and had a recent normal Pap smear. Daily from cycle day 9 until ovulation, then every other day until menses, cervical secretions for IgA, IgG, and cytokines were collected via Weck-cel sponge and serum for luteinizing hormone (LH), estradiol (E), and progesterone was obtained. To control for individual differences in cycle length and time of ovulation, each visit was converted to relative day (RD) to ovulation. From adult data, representative RDs for each cycle phase were identified: RD −4 (follicular), RD 0 (ovulation), RD +8 (luteal). Igs and cytokines were compared among the phases using the Friedman matched samples test. Spearman correlation coefficients (ρ) were used to correlate E levels with Ig and cytokine levels for each phase. Curves were fitted to the data using locally weighted regression (loess) smoothing. Rates of change in IgA and IgG were determined by the slope (β) from linear regressions for the follicular and luteal phases. Mean βs were compared with historical data on 13 adults, using t tests.RESULTS: Three girls (mean age 16.8 years) completed 49 visits (13-23 each). Mean IgA levels varied from 455 μg/mL (RD −4) to 140 μg/mL (RD 0) to 863 μg/mL (RD +8) (p = 0.05), as did mean levels of interleukin (IL)-6 (1756 to 262 to 6200 pg/mL, p = 0.05) and IL-8 (34 to 4 to 59 ng/mL, p = 0.05). Mean IgG levels followed a similar pattern, although the differences were not significant. Loess curves showed that IgA, IgG, IL-2, and IL-8 reached their lowest levels within 1 day of ovulation. In the follicular phase, E levels were negatively correlated with IgA (ρ = −0.62, p = 0.008), IL-2 (ρ = −0.52, p = 0.04), and IL-10 (ρ = −0.70, p = 0.002). Compared with adults, adolescents had a greater drop in IgG in the follicular phase (mean β −953 vs. −269 μg/mL/day, p = 0.045), but a similar rate of rise in IgG in the luteal phase (mean β + 118 vs. +100 μg/mL/day, p = 0.252). Rates of change in IgA did not differ between adolescents and adults for either phase.CONCLUSIONS: Cervical Ig and cytokine levels vary during the menstrual cycle in adolescents, reaching their nadir at ovulation. Adolescents have a steeper decline in follicular IgG than adults, suggesting that adolescents are more immunosuppressed when exposed to unopposed estrogen. Replicating and expanding these findings with a larger sample will be important to develop effective immunoprotection against STDs for this vulnerable population.

Immunoglobulin concentrations and antigen-specific antibody levels in cervicovaginal lavages of rhesus macaques are influenced by the stage of the menstrual cycle.

The levels of antigen-specific antibodies (Abs) and immunoglobulins in the cervical mucus of women vary with the menstrual cycle; the highest levels occur during menses, and the lowest occur during the periovulatory period. The rhesus macaque is a widely used animal model of female genital tract immunity. We sought to determine whether rhesus macaques have a cyclical pattern of changing cervicovaginal Ab and immunoglobulin levels that is similar to that of the human female. This study examined the relationship of the stages of the menstrual cycle to genital mucosal and systemic immunoglobulin concentrations and Ab levels in rhesus macaques. In all seven rhesus macaques studied, the immunoglobulins G and A and some antibodies in cervicovaginal lavages varied with the stages of the menstrual cycle, and in many cases this variation reached the level of statistical significance. In a pattern similar to that of women, the highest levels of Abs and immunoglobulins occurred during menses, and the lowest levels occurred around the time of ovulation. However, the Ab and immunoglobulin levels in serum and rectal lavages did not change with the menstrual cycle stage. The results of this study are consistent with the hypothesis that the ovarian hormones that drive the menstrual cycle influence genital tract immunity in female primates.