Статті в журналах: "Vaginal immunization"

1

Parr, Earl L., and Margaret B. Parr. "Immunoglobulin G, Plasma Cells, and Lymphocytes in the Murine Vagina after Vaginal or Parenteral Immunization with Attenuated Herpes Simplex Virus Type 2." Journal of Virology 72, no. 6 (June 1, 1998): 5137–45. http://dx.doi.org/10.1128/jvi.72.6.5137-5145.1998.

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ABSTRACT This investigation evaluated immunity to vaginal herpes simplex virus type 2 (HSV-2) infection after local or parenteral immunization with attenuated HSV-2. Vaginal immunization induced sterilizing immunity against challenge with a high dose of wild-type virus, whereas parenteral immunizations protected against neurologic disease but did not entirely prevent infection of the vagina. Vaginal immunization caused 86- and 31-fold increases in the numbers of immunoglobulin G (IgG) plasma cells in the vagina at 6 weeks and 10 months after immunization, whereas parenteral immunizations did not increase plasma cell numbers in the vagina. Vaginal secretion/serum titer ratios and specific antibody activities in vaginal secretions and serum indicated that IgG viral antibody was produced in the vagina and released into vaginal secretions at 6 weeks and 10 months after vaginal immunization but not after parenteral immunizations. In contrast to the case for plasma cells, the numbers of T and B lymphocytes in the vagina were similar in vaginally and parenterally immunized mice. Also, lymphocyte numbers in the vagina were markedly but similarly increased by vaginal challenge with HSV-2 in both vaginally and parenterally immunized mice. Lymphocyte recruitment to the vagina after virus challenge appeared to involve memory lymphocytes, because it was not observed in nonimmunized mice. Thus, local vaginal immunization with attenuated HSV-2 increased the number of IgG plasma cells in the vagina and increased vaginal secretion/serum titer ratios to 3.0- to 4.7-fold higher than in parenterally immunized groups but caused little if any selective homing of T and B lymphocytes to the vagina.

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2

Johansson, Eva-Liz, Carola Rask, Margareta Fredriksson, Kristina Eriksson, Cecil Czerkinsky, and Jan Holmgren. "Antibodies and Antibody-Secreting Cells in the Female Genital Tract after Vaginal or Intranasal Immunization with Cholera Toxin B Subunit or Conjugates." Infection and Immunity 66, no. 2 (February 1, 1998): 514–20. http://dx.doi.org/10.1128/iai.66.2.514-520.1998.

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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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3

Wira, C. R., and C. P. Sandoe. "Specific IgA and IgG antibodies in the secretions of the female reproductive tract: effects of immunization and estradiol on expression of this response in vivo." Journal of Immunology 138, no. 12 (June 15, 1987): 4159–64. http://dx.doi.org/10.4049/jimmunol.138.12.4159.

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Abstract Uterine and vaginal secretions collected from intact adult female rats were analyzed to determine whether immunization at sites distal to the reproductive tract had any effect on the presence of specific IgA and IgG antibodies in genital tract secretions. Peyer's patch and i.p. immunization and boost with sheep red blood cells (SRBC) stimulated the appearance of specific IgA antibodies in uterine and vaginal secretions of uterine-ligated animals. IgG antibodies were also induced in uterine but not in vaginal secretions. In contrast, subcutaneous immunization and boost elicited a weak IgA uterine and IgG vaginal response. To establish the role of estradiol in regulating the presence of specific antibodies in the female genital tract, ovariectomized rats received primary and/or secondary Peyer's patch immunizations with hormone treatment. Administration of estradiol daily for 3 days before sacrifice resulted in a significant accumulation of IgA and IgG antibodies to SRBC in uterine secretions. In the absence of estradiol, antibody content was negligible. Vaginal antibody levels were also clearly influenced by estradiol. In contrast to the uterus, however, specific IgA and IgG antibodies were present in the vaginal secretions of saline-injected immunized animals and were markedly inhibited in animals treated with estradiol. These results indicate that antibodies in genital tract secretions can be induced by immunization of the Peyer's patches and that their presence in uterine secretions is clearly dependent on estradiol. Further, they indicate that gut-derived specific antibodies enter the vagina in the absence of hormone stimulation and that estradiol exerts an inhibitory effect on their presence in vaginal secretions.

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4

Eriksson, Kristina, Marianne Quiding-Järbrink, Jacek Osek, Åke Möller, Stellan Björk, Jan Holmgren, and Cecil Czerkinsky. "Specific-Antibody-Secreting Cells in the Rectums and Genital Tracts of Nonhuman Primates following Vaccination." Infection and Immunity 66, no. 12 (December 1, 1998): 5889–96. http://dx.doi.org/10.1128/iai.66.12.5889-5896.1998.

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ABSTRACT To determine optimal strategies to induce specific-antibody-secreting cells (specific ASC) in the rectal and vaginal mucosae, we immunized monkeys with a prototype mucosal immunogen, cholera toxin (CT), given locally or via gastric or parenteral administration. Repeated rectal or vaginal CT immunizations induced strong mucosal and systemic ASC responses. The mucosal responses were, however, confined to the immunization sites and comprised high levels of both specific antitoxin immunoglobulin A (IgA) and IgG. Large numbers of specific IgA and IgG ASC were detected in cell suspensions from dissociated genital and rectal tissues, demonstrating local accumulation of effector B cells at these sites. Intragastric immunization with CT did not per se give rise to cervicovaginal or rectal ASC responses but did prime for a rectal IgA ASC response to local booster immunization. Both rectal and vaginal immunizations also induced circulating blood IgG ASC and IgA ASC. In conclusion, these results show that local administration of antigen to the rectal or vaginal mucosa results in higher ASC responses than systemic or distant mucosal delivery. Furthermore, both the vaginal and the rectal mucosae can serve as inductive sites for systemic ASC responses. These observations should be relevant to the development of vaccines against sexually transmitted diseases such as that caused by human immunodeficiency virus.

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5

Livingston, Julie B., Shan Lu, Harriet Robinson, and Deborah J. Anderson. "Immunization of the Female Genital Tract with a DNA-Based Vaccine." Infection and Immunity 66, no. 1 (January 1, 1998): 322–29. http://dx.doi.org/10.1128/iai.66.1.322-329.1998.

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ABSTRACT Vaccines are being sought for contraception and the prevention of sexually transmitted diseases. However, progress is slow in this area largely because of lack of information on induction of protective immune responses in genital tract mucosa. In this study, we investigated whether in vivo transfection with a model DNA-based antigen delivered by gene gun technology would induce an antibody response detectable in vaginal secretions. Female rats were immunized with plasmids encoding human growth hormone (HGH) under the control of a cytomegalovirus promoter (pCMV/HGH) via vaginal mucosa (V), Peyer’s patch (PP), and/or abdominal skin (S) routes. Localization of HGH in the target tissues demonstrated that all three sites can be transfected in vivo with pCMV/HGH. Vaginal tissues expressed roughly the same level of plasmid as skin. Antibodies to HGH were detectable in serum and vaginal secretions in rats immunized with pCMV/HGH. In the rats primed and boosted vaginally, vaginal immunoglobulin A (IgA) and IgG antibody titers to HGH were sustained for at least 14 weeks, whereas rats immunized via other routes and protocols (S/V, S/S, PP/PP, or PP/V) did not consistently sustain significant vaginal antibody titers beyond week 6. DNA-based immunizations administered by the gene gun may be an effective method of inducing local immunity in the female genital tract.

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6

Wang, Yichuan, Yongjun Sui, Jason Steel, John Morris, and Jay Berzofsky. "Vaginal type-II mucosa acts as an inductive site during the generation of primary CD8+ T cell mucosal immune responses (P3186)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 124.4. http://dx.doi.org/10.4049/jimmunol.190.supp.124.4.

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Abstract It is widely believed that primary immune induction in type-II mucosa (vagina, mouth & cornea) occurs in the draining LNs due to a lack of mucosa-associated lymphoid tissue. In this process, naïve T cells located in the draining LNs are primed by antigen (Ag)-bearing dendritic cells migrating from the Ag-exposed mucosa. Primed T cells then travel to the mucosal site through the bloodstream. In contrast to this paradigm, we show that vaginal mucosa itself can act as an immune inductive site for generation of primary CD8+ T cell mucosal immunity. As evidence, we found that naïve CD8+ T cells routinely migrated to the female reproductive tract and that Ag-specific CD8+ T cells could be generated in the LN-deficient mice after intravaginal immunization. Further, the adoptively transferred naïve OT-1 CD8+ T cells were activated in the vaginal mucosa but not in the draining LNs at 24 hours after intravaginal immunization, even in the presence of FTY720, a drug blocking the egress of T cells from LNs. In addition, the Ag-bearing cells isolated from immunized vaginal mucosa were able to stimulate naïve TCR-transgenic RT-1 CD8+ T cells to secret IFN-γ and undergo proliferation. Finally, vaginal mucosa largely supported the expansion of Ag-specific CD8+ T cells. In conclusion, we present evidence for a new paradigm for primary CD8+ T cell immune induction in type-II mucosa of the vagina, one that occurs locally without the help of draining LNs or mucosa-associated lymphoid tissue.

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7

Medaglini, Donata, Marco R. Oggioni, and Gianni Pozzi. "Vaginal Immunization with Recombinant Gram-Positive Bacteria." American Journal of Reproductive Immunology 39, no. 3 (March 1998): 199–208. http://dx.doi.org/10.1111/j.1600-0897.1998.tb00354.x.

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8

Uehling, David T., Walter J. Hopkins, Jean Jensen, and Edward Balish. "Vaginal Immunization Against Induced Cystitis in Monkeys." Journal of Urology 137, no. 2 (February 1987): 327–29. http://dx.doi.org/10.1016/s0022-5347(17)44015-8.

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9

Hogge, Christopher James, Sabrina Helmold Hait, Gospel Enyindah-Asonye, Zuena Mushtaq, Tanya Hoang, and Marjorie Robert-Guroff. "Replicating Ad-SIV recombinant vaccines elicit mucosal humoral immunity in rhesus macaques at both rectal and vaginal sites with potential protective efficacy." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 72.2. http://dx.doi.org/10.4049/jimmunol.202.supp.72.2.

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Abstract Humoral immunity, especially at mucosal sites, is important for preventing HIV acquisition. Replicating adenovirus (Ad)-SIV priming/gp120 boosting regimens have elicited mucosal immunity and protection against intrarectal SIV challenge in Rhesus macaques. Here we investigated mucosal responses in female macaques primed intranasally/orally, then intratracheally with Ad5hr-SIV(Env/gag/nef), boosted twice intramuscularly with SIV gp120, and challenged vaginally with repeated low-dose SIVmac251. Vaginal washes and rectal swabs and biopsies were obtained 3-weeks post-immunizations. gp120-specific antibodies were assayed by ELISA and memory B-cells by flow cytometry. Gp120-specific rectal memory B-cells increased post-Ad priming but waned post-boosting, whereas rectal and vaginal antibodies increased post-boosting. Compared to pre levels, rectal gp120-specific IgA (p = 0.011) and IgG (p< 0.0001) were elevated post-2nd boost; vaginal IgA/IgG antibodies differed post-1st boost (both p<0.0001) and IgG levels > IgA post-2nd boost (p=0.001). Rectal memory B cells post- 1st and 2nd Ads positively correlated with gp120-specific rectal IgA (p = 0.015, p = 0.0013, respectively) post-1st Ad, indicating vaccine targeting to mucosal effector sites. Significantly delayed SIV acquisition was not seen, but vaginal IgG post-1st Ad correlated with number of challenges (p=0.029). Vaccinated animals had lower acute viremia than controls (p = 0.054), consistent with higher vaginal gp120-specific IgG 2 weeks post-infection (p < 0.0001). Our data show that upper respiratory tract immunization with replicating Ad vectors elicits strong mucosal immunity with potential protective efficacy against rectal/genital transmission.

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10

Hymel, Terri J., Joseph Sherman, Sandra K. Pope, and Kelly J. Kelleher. "Inadequate Immunizations." Clinical Pediatrics 32, no. 3 (March 1993): 156–60. http://dx.doi.org/10.1177/000992289303200306.

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Immunizations are cost-effective measures for assuring public health. However, recent outbreaks of measles, mumps, and pertussis underscore the inadequacy of current immunization programs. A model identifying those children who are likely to be inadequately immunized could focus the use of limited health funds. A retrospective examination of the medical charts of 101 children in a large inner-city clinic was undertaken to determine if specific factors were associated with inadequate immunization status. Fifty percent of the children were inadequately immunized by 18 months of age (no measles-mumps-rubella or fewer than three diphtheria-pertussis-tetanus vaccinations). Logistic regression analyses showed that older maternal age, no recurrent or chronic illnesses, and vaginal delivery were independently associated with inadequate immunization status. However, on many charts, information on maternal, social, and environmental variables was incomplete. The increasing use of structured medical charts will enhance data collection and the determination of an appropriate index. A prospective study of the variables identified, along with standardization of medical records and inclusion of social history data, is necessary to further investigate the utility of screening criteria for inadequate immunizations.

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11

Jersey, James de, Lyn A. Hinds та Mark P. Bradley. "Regulation of reproductive tract immunoglobulins by oestradiol-17β in the European Red Fox (Vulpes vulpes)". Reproduction, Fertility and Development 9, № 5 (1997): 531. http://dx.doi.org/10.1071/r97035.

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The effect of the ovarian hormone, oestradiol-17β, on reproductive tract immunity in the female fox was investigated. Reproductive tract antibody responses were induced by either Peyer’s patch immunization with a recombinant fox sperm protein, or by oral immunization with live, attenuated Salmonella typhimurium. The effect of exogenous oestradiol-17β or the stage of the oestrous cycle on reproductive tract immunity was assessed. The secretion of specific vaginal IgA, but not vaginal IgG, antibodies was reduced by exogenous treatment with oestradiol-17β, while both specific vaginal IgA and vaginal IgG levels declined during the period of natural oestrus. It is concluded that oestradiol-17β, and probably other reproductive hormones, are involved in the regulation of antibody-secretion in the fox reproductive tract, and that reproductive status is an important factor to consider in the design and application of vaccines which aim to induce immunity within the female reproductive tract.

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12

Gillgrass, Amy E., Vera A. Tang, Kate M. Towarnicki, Kenneth L. Rosenthal, and Charu Kaushic. "Protection against Genital Herpes Infection in Mice Immunized under Different Hormonal Conditions Correlates with Induction of Vagina-Associated Lymphoid Tissue." Journal of Virology 79, no. 5 (March 1, 2005): 3117–26. http://dx.doi.org/10.1128/jvi.79.5.3117-3126.2005.

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ABSTRACT The present study was undertaken to examine the effect of the hormonal environment on immunization with an attenuated strain of herpes simplex virus type 2 (HSV-2 TK−) and subsequent protection against challenge. Ovariectomized mice were administered saline (S; control), estradiol (E2), progesterone (P4), or a combination of estradiol and progesterone (E+P) and immunized intravaginally (IVAG) with HSV-2 TK−. Three weeks later, the immunized mice were challenged IVAG with wild-type HSV-2. Mice that were immunized following E treatment were not protected, whereas complete protection against the challenge was seen in mice from the S- and P4-treated groups. In the P4-treated group, 15% of mice developed chronic pathology following TK− immunization. Interestingly, about 40% of the E+P-treated mice were also protected. Upon examination of viral shedding in the vaginal secretions, it was clear that protection against challenge was dependent on the ability of the TK− virus to cause productive genital infection under different hormonal conditions. In the protected mice (the S and P groups and part of the E+P group), induced vagina-associated lymphoid tissues composed of CD11c+ dendritic cells and CD3+ and CD4+ T cells were formed transiently in the vaginal lamina propria from day 2 to day 5 postchallenge. These aggregates were absent in the unprotected mice (the E group and part of the E+P group). Significant HSV-2-specific activation of lymphocytes was observed in the local draining lymph nodes of protected mice. This response was absent in the unprotected groups. High titers of gB-specific local immunoglobulin A (IgA) antibodies were present in the vaginal secretions of S- and P4-treated immunized mice following HSV-2 challenge. The S-treated group of mice also had high gB-specific IgG titers. These studies show that sex hormones modify the induction of protective immune responses following IVAG immunization.

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Tucker, Kiersten, Veronica Dave, and Jennifer M. Lund. "Mucosal vaccination provides protection from HSV-2 infection and disease." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 64.07. http://dx.doi.org/10.4049/jimmunol.208.supp.64.07.

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Abstract Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that is estimated to infect around 23 million people per year. Despite high global prevalence, there are not any approved vaccines that are therapeutic or preventative. Most vaccines that we use today rely on injecting antigens intramuscularly in order to elicit an adaptive immune response. However, given that most pathogens gain entry to the host across barrier surfaces, a focus on eliciting mucosal immunity may enhance protection; vaccine-induced local immunity at the site of first pathogen exposure may have the best chance at preventing the spread of infection beyond the pathogen portal of entry. We hypothesized that a mucosal immunization would prime memory T cells to reside in vaginal tissues and provide better protection against vaginal HSV-2 exposure than other routes of immunization. Our initial data suggests that intranasal immunization is effective in protecting mice from vaginal HSV-2 infection. Ongoing work focuses on characterizing the role of vaccine-elicited mucosal CD8+ T cells in preventing infection to provide insight into the mechanisms of protection induced by mucosal immunization for HSV-2. These findings contribute to the efforts to generate an effective vaccine to prevent HSV-2 infection and disease. Supported by the Mary Gates Research Scholarship and the Art Levinson Award through the University of Washington.

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14

Whaley, K. J., L. Zeitlin, R. A. Barratt, T. E. Hoen, and R. A. Cone. "Passive Immunization of the Vagina Protects Mice against Vaginal Transmission of Genital Herpes Infections." Journal of Infectious Diseases 169, no. 3 (March 1, 1994): 647–49. http://dx.doi.org/10.1093/infdis/169.3.647.

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15

Xiang, Zhi Quan, Susanna Pasquini, and Hildegund C. J. Ertl. "Induction of Genital Immunity by DNA Priming and Intranasal Booster Immunization with a Replication-Defective Adenoviral Recombinant." Journal of Immunology 162, no. 11 (June 1, 1999): 6716–23. http://dx.doi.org/10.4049/jimmunol.162.11.6716.

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Abstract Mice immunized through different routes such as i.m., intradermally, or intratracheally with a DNA vaccine to rabies virus developed high titers of serum Ab but only borderline levels of mucosal Abs determined from vaginal secretions. DNA vaccines given by either route enhanced vaginal IgA and IgG2a secretion upon a subsequent intranasal booster immunization with an E1-deleted adenoviral recombinant expressing the same Ag of rabies virus. DNA vaccine priming reduced the Ab response to the adenoviral Ags and counterbalanced the impaired B cell response to the rabies virus Ag expressed by the adenoviral recombinant in mice preimmune to adenovirus. The vaginal B cell response could further be enhanced by using the Th2-type cytokines IL-4 or IL-5 as genetic adjuvants concomitantly with the DNA vaccine before intranasal booster immunization with the recombinant vaccine.

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16

Staats, H. F., W. G. Nichols, and T. J. Palker. "Mucosal immunity to HIV-1: systemic and vaginal antibody responses after intranasal immunization with the HIV-1 C4/V3 peptide T1SP10 MN(A)." Journal of Immunology 157, no. 1 (July 1, 1996): 462–72. http://dx.doi.org/10.4049/jimmunol.157.1.462.

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Abstract To optimize mucosal immune responses to the HIV-1 peptide vaccine candidate T1SP10 MN(A), we intranasally immunized BALB/c and C57BL/6 mice with C4/V3 HIV-1 peptide together with the mucosal adjuvant cholera toxin (CT). Four doses over a 4-wk period resulted in peak serum anti-peptide IgG titers of > 1:160,000 in BALB/c mice and > 1:520,000 in C57BL/6 mice, and significant levels (>1:30,000) persisted in both strains of mice for longer than 6 mo. Furthermore, intranasal immunization with peptide and CT induced serum IgG reactivity to HIV-1 gp120 and HIV-1(MN) neutralizing responses. The primary anti-peptide IgG subclass was IgG1, suggesting a predominant Th2-type response. In addition to elevated serum anti-peptide A responses, intranasal immunization with T1SP10 MN(A) and CT induced both vaginal anti-peptide IgG and IgA responses, which persisted for 91 days in both strains of mice. Vaginal anti-HIV IgA was frequently associated with secretory component, suggesting transepithelial transport of IgA into vaginal secretions. Cervical lymph nodes contained the highest relative concentration of anti-T1SP10 MN(A) IgG-producing cells, while the spleen was the next major site of anti-T1SP10 MN(A) IgG-producing cells. Ag-specific proliferative responses were also detected in cervical lymph node and spleen cell populations after intranasal immunization with T1SP10 MN(A) and CT. In addition, intranasal immunization with T1SP10 MN(A) and CT was able to induce anti-HIV cell-mediated immunity in vivo as indicated by the induction of delayed-type hypersensitivity. Therefore, intranasal immunization with hybrid HIV peptides provides a noninvasive route of immunization that induces both long-lived systemic and mucosal Ab responses as well as cell-mediated immunity to HIV.

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Shillova, Nita, Savannah E. Howe, Besmir Hyseni, Deahneece Ridgell, Derek J. Fisher, and Vjollca Konjufca. "Chlamydia-Specific IgA Secretion in the Female Reproductive Tract Induced via Per-Oral Immunization Confers Protection against Primary Chlamydia Challenge." Infection and Immunity 89, no. 1 (November 2, 2020): e00413-20. http://dx.doi.org/10.1128/iai.00413-20.

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ABSTRACTChlamydia trachomatis is an obligate intracellular pathogen that causes sexually transmitted disease. In women, chlamydial infections may cause pelvic inflammatory disease (PID), ectopic pregnancy, and infertility. The role of antibodies in protection against a primary Chlamydia infection is unclear and was a focus of this work. Using the C. muridarum mouse infection model, we show that intestinal mucosa is infected via intranasal (i.n.) or per-oral (p.o.) Chlamydia inoculation and that unlike the female reproductive tract (FRT) mucosa, it halts systemic Chlamydia dissemination. Moreover, p.o. immunization or infection with Chlamydia confers protection against per-vaginal (p.v.) challenge, resulting in significantly decreased bacterial burden in the FRT, accelerated Chlamydia clearance, and reduced hydrosalpinx pathology. In contrast, subcutaneous (s.c.) immunization conferred no protection against the p.v. challenge. Both p.o. and s.c. immunizations induced Chlamydia-specific serum IgA. However, IgA was found only in the vaginal washes and fecal extracts of p.o.-immunized animals. Following a p.v. challenge, unimmunized control and s.c.-s.c.-immunized animals developed Chlamydia-specific intestinal IgA yet failed to develop IgA in the FRT, indicating that IgA response in the FRT relies on the FRT to gastrointestinal tract (GIT) antigen transport. Vaginal secretions of p.o.-immunized animals neutralize Chlamydia in vivo, resulting in significantly lower Chlamydia burden in the FRT and Chlamydia transport to the GIT. We also show that infection of the GIT is not necessary for induction of protective immunity in the FRT, a finding that is important for the development of p.o. subunit vaccines to target Chlamydia and possibly other sexually transmitted pathogens.

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Dupuy, Catherine, Dominique Buzoni-Gatel, Antoine Touzé, Daniel Bout, and Pierre Coursaget. "Nasal Immunization of Mice with Human Papillomavirus Type 16 (HPV-16) Virus-Like Particles or with the HPV-16 L1 Gene Elicits Specific Cytotoxic T Lymphocytes in Vaginal Draining Lymph Nodes." Journal of Virology 73, no. 11 (November 1, 1999): 9063–71. http://dx.doi.org/10.1128/jvi.73.11.9063-9071.1999.

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ABSTRACT Human papillomavirus type 16 (HPV-16) infects the genital tract and is closely associated with the development of cervical cancer. HPV-16 initiates infection at the genital mucosal surface; thus, mucosal immune responses are likely to contribute to defense against HPV-16 infection. However, little information is available regarding the induction of immune responses in the genital tract mucosa. In this study, we evaluated the potential of intranasally administered papillomavirus vaccines to elicit both systemic and vaginal immune responses. HPV-16 virus-like particles (VLPs) produced by self-assembly of L1 protein and the HPV-16 L1 gene cloned into a mammalian expression vector were used as vaccines. Intranasally administered VLPs induced serum immunoglobulin G (IgG) and vaginal IgA secretory antibodies. Very weak serum IgG and vaginal IgA responses were found after DNA immunization. Both splenic and vaginal lymphocytes could be activated by intranasal immunization with VLPs and the HPV-16 L1 gene. Activated CD4+ Th1-like T cells were shown to synthesize gamma interferon, and activated CD8+ T cells were demonstrated to be cytotoxic.

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Kutzler, Michele, Noshin Kathuria, Ashley Curatola, Getrude Makurumidze, Devon Myles, Kar Muthumani, Albert Sylvester, et al. "CCR10 expression is required for immunogenicity of a HIV-1env DNA vaccine encoding CCL28 to enhance HIV-1env-specific IgG and IgA at relevant mucosal sites (VAC7P.986)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 141.31. http://dx.doi.org/10.4049/jimmunol.192.supp.141.31.

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Abstract Development of a vaccine that drives anti-viral mucosal B cell responses is critical for protection against HIV-1 infection. It is currently unknown whether triggering CCR10/CCL28 pathways in a DNA-based vaccine results in induction of HIV-1env specific B cell immunity at mucosal sites of infection. We hypothesized that co-immunization with HIV-1env/CCL28 molecular adjuvant would augment B cell responses at gastrointestinal and vaginal sites and require CCR10. CCL28 co-immunized WT mice displayed a significant enhancement of HIV-1env specific antibody titers in serum, feces and vaginal washes, and enhanced HIV-1 specific IgA responses were abrogated in CCR10KO mice. CCL28 co-immunization did not increase the breadth of linear B cell epitopes in WT mice, but augmented the dominant epitopes elicited by antigen immunization alone. The frequency of splenic and intestinal IgA+CD19+B220+CD138+CCR10+ plasmablasts was augmented in the CCL28 co-immunized WT mice over antigen-only immunized WT controls. The physiological relevance of these findings was confirmed in a NHP model of intravaginal SIVsmE660 challenge in which CCL28 co-immunization resulted in significant increases in serum/vaginal IgG/IgA, decrease in peak viral loads, significant suppression of viral titers over 120 days, and recovery of CD4 T cells. These data support a role for CCL28 in targeting protective anti-viral B cells to mucosal sites when delivered as molecular adjuvants for HIV-1env DNA-based vaccines.

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Matchett, William E., Goda Baddage Rakitha Malewana, Haley Mudrick, Michael J. Medlyn, and Michael A. Barry. "Genetic Adjuvants in Replicating Single-Cycle Adenovirus Vectors Amplify Systemic and Mucosal Immune Responses against HIV-1 Envelope." Vaccines 8, no. 1 (February 2, 2020): 64. http://dx.doi.org/10.3390/vaccines8010064.

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Most infections occur at mucosal surfaces. Providing a barrier of protection at these surfaces may be a useful strategy to combat the earliest events in infection when there are relatively few pathogens to address. The majority of vaccines are delivered systemically by the intramuscular (IM) route. While IM vaccination can drive mucosal immune responses, mucosal immunization at intranasal (IN) or oral sites can lead to better immune responses at mucosal sites of viral entry. In macaques, IN immunization with replicating single-cycle adenovirus (SC-Ads) and protein boosts generated favorable mucosal immune responses. However, there was an apparent “distance effect” in generating mucosal immune responses. IN immunization generated antibodies against HIV envelope (env) nearby in the saliva, but weaker responses in samples collected from the distant vaginal samples. To improve on this, we tested here if SC-Ads expressing genetic adjuvants could be used to amplify antibody responses in distant vaginal samples when they are codelivered with SC-Ads expressing clade C HIV env immunogen. SC-Ads env 1157 was coadministered with SC-Ads expressing 4-1BBL, granulocyte macrophage colony-stimulating factor (GMCSF), IL-21, or Clostridoides difficile (C. diff.) toxin fragments by IN or IM routes. These data show that vaginal antibody responses were markedly amplified after a single immunization by the IN or IM routes, with SC-Ad expressing HIV env if this vaccine is complemented with SC-Ads expressing genetic adjuvants. Furthermore, the site and combination of adjuvants appear to “tune” these antibody responses towards an IgA or IgG isotype bias. Boosting these priming SC-Ad responses with another SC-Ad or with SOSIP native-like env proteins markedly amplifies env antibody levels in vaginal washes. Together, this data may be useful in informing the choice of route of delivery adenovirus and peptide vaccines against HIV-1.

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Klavinskis, L. S., L. A. Bergmeier, L. Gao, E. Mitchell, R. G. Ward, G. Layton, R. Brookes, N. J. Meyers, and T. Lehner. "Mucosal or targeted lymph node immunization of macaques with a particulate SIVp27 protein elicits virus-specific CTL in the genito-rectal mucosa and draining lymph nodes." Journal of Immunology 157, no. 6 (September 15, 1996): 2521–27. http://dx.doi.org/10.4049/jimmunol.157.6.2521.

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Abstract The major routes of HIV transmission are through the rectal and cervico-vaginal mucosa. To prevent dissemination of HIV to the regional lymph nodes (LNs), an effective vaccine may need to stimulate CTL in the rectal or genital tract and the draining LNs. We report that mucosal immunization by the recto-oral and vagino-oral route or s.c. immunization targeting the iliac LNs with a particulate SIVp27:Ty-VLP vaccine elicits SIVgag-specific CTL in the regional LNs as well as in the spleen and PBMC. Targeted LN immunization with this vaccine elicited MHC class I-restricted CD8+ CTL responses, and the highest frequency of CTL was found in the iliac LNs. Moreover, SIVgag-specific CTL activity was detected in short term T cell lines established in mononuclear cells eluted from the rectal and cervico-vaginal mucosa. The relative frequency of CTL in short term cell lines prepared from the rectal mucosa (21/113 or 18.6%) was similar to that obtained from the cervico-vaginal mucosa (16/79 or 20.3%). Examination of the relative frequency of CTL to the T cell epitopes residing within SIVp27 showed a higher frequency in iliac LN cells to peptide aa 41-70 than in that to peptide aa 121-150, and this was significant after both recto-oral (chi-squared 6.500, p < 0.02) and vagino-oral (chi-squared = 10.391, p < 0.01) immunization. In contrast, the relative frequency of CTL in PBMC to peptide aa 41-70 (15.5%) was comparable to that elicited by peptide aa 121-150 (17.6%). This study provides novel evidence that mucosal or targeted LN immunization can generate anti-SIV CTL in the rectal and genital mucosa, in the draining LNs, and in the central lymphoid system.

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Shen, Xuzhuang, Teresa Lagergård, Yonghong Yang, Marianne Lindblad, Margareta Fredriksson, and Jan Holmgren. "Systemic and Mucosal Immune Responses in Mice after Mucosal Immunization with Group B Streptococcus Type III Capsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccine." Infection and Immunity 68, no. 10 (October 1, 2000): 5749–55. http://dx.doi.org/10.1128/iai.68.10.5749-5755.2000.

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ABSTRACT Group B streptococci (GBS) colonize the female genital and rectal tracts and can cause invasive infection in susceptible newborns. An optimally effective GBS vaccine should induce mucosal and systemic immunity. In this study, we investigate the local and systemic immune responses to GBS type III capsular polysaccharide (CPS) after mucosal vaccination of mice via intranasal, peroral, rectal, and vaginal routes, with GBS type III CPS conjugated with recombinant cholera toxin B subunit (GBS III CPS-rCTB). Cholera toxin (CT) was added as an adjuvant. Immunoglobulin G (IgG) and IgA antibodies to the CPS were tested in serum, lungs, and intestinal, rectal, and vaginal extracts by enzyme-linked immunosorbent assay. The conjugated CPS administered by intranasal, peroral, rectal, and vaginal routes was much more effective at inducing both mucosal and systemic antibody responses to GBS III CPS than was unconjugated CPS. The CPS-specific immune responses in various organs were dependent on the route of immunization. Generally, the highest levels of IgA and IgG were generated in the regions or sites of the conjugate exposure. Thus, intranasal vaccination elicited the highest anti-CPS IgA and IgG antibody levels in the lungs, whereas peroral administration in the intestinal site and vaginal vaccination elicited the highest antibody levels in the vagina. Rectal vaccination was superior to the other routes in inducing high antibody levels in the rectum. The four routes of mucosal vaccination also induced distant antibody responses to CPS. Rectal vaccination induced high specific IgA levels in the vagina and intestine, and oral administration induced high specific IgA levels in the lungs and rectum. All four routes of vaccination with the conjugate elicited similarly high levels of anti-CPS IgG in serum. Intranasal vaccination with different doses of the conjugate (10, 30, and 80 μg of CPS) did not have a significant influence on the anti-CPS specific antibody responses. Intranasal immunization induced better antibody responses when one dose of the conjugate was divided and given on three consecutive days compared to administration of the full dose on one occasion. In conclusion, rectal and vaginal vaccination may be the best way of stimulating anti-CPS immune responses in the rectal and vaginal tracts, while high levels of anti-CPS antibodies in the lungs can be achieved after intranasal administration. The vaccination regimen thus might influence the mucosal immune response to CPS. This conjugate may serve as an effective mucosal vaccine for preventing mucosal colonization and invasive infection caused by GBS.

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Hillier, Sharon L., Patricia Ferrieri, Morven S. Edwards, Marian Ewell, Daron Ferris, Paul Fine, Vincent Carey, et al. "A Phase 2, Randomized, Control Trial of Group B Streptococcus (GBS) Type III Capsular Polysaccharide-tetanus Toxoid (GBS III-TT) Vaccine to Prevent Vaginal Colonization With GBS III." Clinical Infectious Diseases 68, no. 12 (October 3, 2018): 2079–86. http://dx.doi.org/10.1093/cid/ciy838.

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Abstract Background Group B Streptococcus (GBS) frequently colonizes pregnant women and can cause sepsis and meningitis in young infants. If colonization was prevented through maternal immunization, a reduction in perinatal GBS disease might be possible. A GBS type III capsular polysaccharide (CPS)-tetanus toxoid conjugate (III-TT) vaccine was evaluated for safety and efficacy in preventing acquisition of GBS colonization. Methods Healthy, nonpregnant women aged 18–40 years and screened to be GBS III vaginal and rectal culture negative were randomized to receive III-TT conjugate or tetanus diphtheria toxoid vaccine in a multicenter, observer-blinded trial. GBS vaginal and rectal cultures and blood were obtained bimonthly over 18 months. Serum concentrations of GBS III CPS-specific antibodies were determined using enzyme-linked immunosorbent assay. Results Among 1525 women screened, 650 were eligible for the intent-to-treat analysis. For time to first acquisition of vaginal GBS III, vaccine efficacy was 36% (95% confidence interval [CI], 1%–58%; P = .044), and for first rectal acquisition efficacy was 43% (95% CI, 11% to 63%; P = .014). Two months post-immunization, geometric mean concentrations of serum GBS type III CPS-specific immunoglobulin G were 12.6 µg/mL (95% CI, 9.95 to 15.81) in GBS III-TT recipients, representing a 4-fold increase from baseline in 95% of women, which persisted. Both vaccines were well tolerated. Conclusions GBS CPS III-TT conjugate vaccine significantly delayed acquisition of vaginal and rectal GBS III colonization. In addition to its use for maternal immunization to passively protect infants with maternally derived antibodies, a multivalent vaccine might also serve to reduce fetal and neonatal exposure to GBS. Clinical Trials Registration NCT00128219.

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Pettini, Elena, Gennaro Prota, Annalisa Ciabattini, Alessandro Boianelli, Fabio Fiorino, Gianni Pozzi, Antonio Vicino, and Donata Medaglini. "Vaginal Immunization to Elicit Primary T-Cell Activation and Dissemination." PLoS ONE 8, no. 12 (December 5, 2013): e80545. http://dx.doi.org/10.1371/journal.pone.0080545.

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De Bernardis, Flavia, Maria Boccanera, Daniela Adriani, Antonietta Girolamo, and Antonio Cassone. "Intravaginal and Intranasal Immunizations Are Equally Effective in Inducing Vaginal Antibodies and Conferring Protection against Vaginal Candidiasis." Infection and Immunity 70, no. 5 (May 2002): 2725–29. http://dx.doi.org/10.1128/iai.70.5.2725-2729.2002.

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ABSTRACT Oophorectomized, estrogen-treated rats were immunized by the intravaginal or intranasal route with a mannoprotein extract (MP) or secreted aspartyl proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal adjuvant. Both routes of immunization were equally effective in (i) inducing anti-MP and anti-Sap vaginal antibodies and (ii) conferring a high degree of protection against the vaginal infection by the fungus. These data suggest that appropriate fungal antigens and adjuvant can be used to protect against candidal vaginitis, by either route.

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Li, Guocai, Hongmei Jiao, Guihua Jiang, Jing Wang, Litian Zhu, Rushan Xie, Hua Yan, Hongju Chen, and Mingchun Ji. "Neisseria gonorrhoeae NspA Induces Specific Bactericidal and Opsonic Antibodies in Mice." Clinical and Vaccine Immunology 18, no. 11 (September 14, 2011): 1817–22. http://dx.doi.org/10.1128/cvi.05245-11.

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ABSTRACTNeisseria gonorrhoeaesurface protein A (NspA) is a highly conserved gonococcal antigen. To explore the potential of NspA in vaccine development against gonorrhea, BALB/c mice were immunized with pcNspA containing the NspA gene fromN. gonorrhoeaestrain WHO-A via intramuscular (i.m.) injection, intranasal (i.n.) immunization, or intravaginal (i.vag.) immunization. Following the last DNA immunization, mice were boosted with recombinant NspA (rNspA). Enzyme-linked immunosorbent assays (ELISAs) indicated that all immunized mice generated measurable NspA-specific IgG and IgA in serum and secretory IgA (sIgA) in vaginal wash fluids. The antisera had bactericidal and opsonic activities. These data demonstrated that NspA induced antibodies with antigonococcal activity.

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Vagvala, Sri P., Lydia G. Thebeau, Saydra R. Wilson, and Lynda A. Morrison. "Virus-Encoded B7-2 Costimulation Molecules Enhance the Protective Capacity of a Replication-Defective Herpes Simplex Virus Type 2 Vaccine in Immunocompetent Mice." Journal of Virology 83, no. 2 (November 5, 2008): 953–60. http://dx.doi.org/10.1128/jvi.02022-08.

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ABSTRACT Herpes simplex virus 2 (HSV-2) and, to a lesser extent, HSV-1 cause the majority of sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective HSV stimulates immune responses in animals but produces no progeny virus, making it potentially useful as a safe form of live vaccine against HSV. Because it does not replicate and spread in the host, however, replication-defective virus may have relatively limited capacity to solicit professional antigen presentation. We previously demonstrated that in mice devoid of B7-1 and B7-2 costimulation molecules, replication-defective HSV-2 encoding B7-1 or B7-2 induces stronger immune responses and protection against HSV-2 challenge than immunization with replication-defective virus alone. Here, we vaccinated wild-type mice fully competent to express endogenous B7 costimulation molecules with replication-defective HSV-2 or replication-defective virus encoding B7-2 and compared their capacities to protect against vaginal HSV-2 infection and disease. Replication-defective virus encoding B7-2 induced more IFN-γ-producing CD4 T cells than did replication-defective virus alone. Immunization with B7-2-expressing virus decreased challenge virus replication in the vaginal mucosa, genital and neurological disease, and mortality more effectively than did immunization with the parental replication-defective virus. Prior immunization with B7-expressing, replication-defective virus also effectively suppressed infection of the nervous system compared to immunization with the parental virus. Thus, B7 costimulation molecules expressed at the site of HSV infection can enhance vaccine efficacy even in a fully immunocompetent host.

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Garulli, Bruno, Yoshihiro Kawaoka, and Maria R. Castrucci. "Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus." Journal of Virology 78, no. 2 (January 15, 2004): 1020–25. http://dx.doi.org/10.1128/jvi.78.2.1020-1025.2004.

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ABSTRACT The humoral and cellular immune responses in the genital mucosa likely play an important role in the prevention of sexually transmitted infections, including infection with human immunodeficiency virus type 1 (HIV-1). Here we show that vaginal infection of progesterone-treated BALB/c mice with a recombinant influenza virus bearing the immunodominant P18IIIB cytotoxic T-lymphocyte (CTL) epitope of the gp160 envelope protein from an HIV-1 IIIB isolate (P18IIIB; RIQRGPGRAFVTIGK) can induce a specific immune response in regional mucosal lymph nodes, as well as in a systemic site (the spleen). A single inoculation of mice with the recombinant influenza virus induced long-lasting (at least 5 months) antigen-specific CTL memory detectable as a rapid recall of effector CTLs upon vaginal infection with recombinant vaccinia virus expressing HIV-1 IIIB envelope gene products. Long-term antigen-specific CTL memory was also induced and maintained in distant mucosal tissues when mice were intranasally immunized with the recombinant influenza virus. These results indicate that mucosal immunization and, in particular, local vaginal immunization with recombinant influenza virus can provide strong, durable immune responses in the female genital tract of mice.

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Wassen, Lotta, and Marianne Jertborn. "Influence of Exogenous Reproductive Hormones on Specific Antibody Production in Genital Secretions after Vaginal Vaccination with Recombinant Cholera Toxin B Subunit in Humans." Clinical and Vaccine Immunology 13, no. 2 (February 2006): 202–7. http://dx.doi.org/10.1128/cvi.13.2.202-207.2006.

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ABSTRACT The objective of this study was to investigate the influence of exogenous reproductive hormones on the local and systemic production of specific immunoglobulin A (IgA) and IgG antibodies after vaginal vaccination with recombinant cholera toxin subunit B (CTB). Three groups of women using either progesterone-containing intrauterine devices (n = 9), oral contraceptives (n = 8), or no hormonal contraceptive methods (n = 9) were vaginally immunized twice, 2 weeks apart. Cervical secretions, vaginal fluids, and serum were collected before and after vaccination. Total and CTB-specific IgA and IgG antibodies in genital secretions and serum were analyzed by enzyme-linked immunosorbent assay. A majority of the women presented strong CTB-specific IgA and IgG antibody responses in cervicovaginal secretions after vaccination, whereas the antitoxin responses in serum were weaker. Exogenously administered steroid hormones did not seem to have any impact on the production of specific antibodies. Both the frequencies and the magnitudes of IgA and IgG antitoxin responses in genital secretions were comparable among the three immunization groups. An association, in particular for IgA, was found between the magnitudes of the CTB-specific antibody responses in cervical secretions and vaginal fluids after vaccination. The sensitivities and positive predictive values of vaginal antibody analyses to reflect responses in cervical secretions were also high, suggesting that vaginal fluids alone might be used for evaluation of genital immune responses in large-scale vaccination studies in the future.

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VanCott, Thomas C., Robert W. Kaminski, John R. Mascola, Vaniambadi S. Kalyanaraman, Nabila M. Wassef, Carl R. Alving, J. Terry Ulrich, George H. Lowell, and Deborah L. Birx. "HIV-1 Neutralizing Antibodies in the Genital and Respiratory Tracts of Mice Intranasally Immunized with Oligomeric gp160." Journal of Immunology 160, no. 4 (February 15, 1998): 2000–2012. http://dx.doi.org/10.4049/jimmunol.160.4.2000.

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Abstract Because mucosal surfaces are a primary route of HIV-1 infection, we evaluated the mucosal immunogenicity of a candidate HIV-1 vaccine, oligomeric gp160 (o-gp160). In prior studies, parenteral immunization of rabbits with o-gp160 elicited broad neutralizing serum Ab responses against both T cell line-adapted HIV-1 and some primary HIV-1 isolates. In this study, nasal immunization of mice with o-gp160, formulated with liposomes containing monophosphoryl lipid A (MPL), MPL-AF, proteosomes, emulsomes, or proteosomes with emulsomes elicited strong gp160-specific IgG and IgA responses in serum as well as vaginal, lung, and intestinal washes and fecal pellets. The genital, respiratory, and intestinal Abs were determined to be locally produced. No mucosal immune responses were measurable when the immunogen was given s.c. Abs from sera and from vaginal and lung washes preferentially recognized native forms of monomeric gp120, suggesting no substantial loss in protein tertiary conformation after vaccine formulation and mucosal administration. Inhibition of HIV-1MN infection of H9 cells was found in sera from mice immunized intranasally with o-gp160 formulated with liposomes plus MPL, proteosomes, and proteosomes plus emulsomes. Formulations of o-gp160 with MPL-AF, proteosomes, emulsomes, or proteosomes plus emulsomes elicited HIV-1MN-neutralizing Ab in lung wash, and formulations with proteosomes, emulsomes, or proteosomes plus emulsomes elicited HIV-1MN-neutralizing Ab in vaginal wash. These data demonstrate the feasibility of inducing both systemic and mucosal HIV-1-neutralizing Ab by intranasal immunization with an oligomeric gp160 protein.

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Kuklin, Nelly A., Massoud Daheshia, Sangjun Chun, and Barry T. Rouse. "Role of Mucosal Immunity in Herpes Simplex Virus Infection." Journal of Immunology 160, no. 12 (June 15, 1998): 5998–6003. http://dx.doi.org/10.4049/jimmunol.160.12.5998.

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Abstract This study evaluates whether the vaginal mucosal surface of immunized mice can prevent invasion by herpes simplex virus (HSV) and aims to identify immune components that affect immunity after challenge at the vaginal mucosa. Despite the induction of both IgA and IgG vaginal Ab following immunization with recombinant vaccinia virus vectors expressing either glycoproteins B or D, viral infection occurred in most animals even after minimal viral dose challenge. Challenged immune animals, including those genetically unable to generate anti-HSV Ab, survived and showed few if any clinical signs of infection. Experiments with T cell subtype knockout animals and depletion with T cell subset-specific MAb indicated that immunity following vaginal challenge was principally dependent on the function of CD4+ T cells. Our results indicate that anti-HSV vaccines may not provide barrier immunity at the vaginal mucosal site but may be adequate to minimize clinical expression of disease.

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Li, Weidang, Ashlesh K. Murthy, M. Neal Guentzel, James P. Chambers, Thomas G. Forsthuber, J. Seshu, Guangming Zhong, and Bernard P. Arulanandam. "Immunization with a Combination of Integral Chlamydial Antigens and a Defined Secreted Protein Induces Robust Immunity against Genital Chlamydial Challenge." Infection and Immunity 78, no. 9 (July 6, 2010): 3942–49. http://dx.doi.org/10.1128/iai.00346-10.

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ABSTRACT We have previously demonstrated the efficacy of recombinant chlamydial protease-like activity factor (rCPAF; a secreted chlamydial protein) in inducing antigen-specific CD4+ T cell/gamma interferon (IFN-γ)-mediated but not antibody-mediated chlamydial clearance and reduction of upper genital tract (UGT) pathological sequelae. Since chlamydial integral antigens may induce neutralizing antibody protection, we further evaluated induction of protective immunity using a combination of rCPAF and UV-inactivated chlamydial elementary bodies (UV-EB) against vaginal chlamydial challenge in comparison to immunization with the individual components or live EB. The rCPAF-UV-EB immunization induced a significantly enhanced anti-UV-EB cellular and antibody response and a reduced anti-CPAF cellular and antibody response, compared to immunization with the respective individual components. Moreover, vaccination with UV-EB and rCPAF-UV-EB induced serum antibodies that neutralized chlamydial infectivity. The rCPAF-UV-EB immunization resulted in a significant reduction of vaginal chlamydial shedding and induced earlier bacterial clearance than vaccination of mice with the individual components. Importantly, the UGT sequelae were significantly reduced in mice immunized with rCPAF or rCPAF-UV-EB, but not in those immunized with UV-EB alone, and approached the levels of protection induced by live EB. These results collectively suggest that a combination of neutralizing antibodies induced by integral chlamydial antigens and cell-mediated responses induced by secreted proteins such as CPAF induces optimal protective immunity against genital chlamydial infections.

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Uehling, David T., Walter J. Hopkins, and Edward Balish. "Decreased Immunologic Responsiveness Following Intensified Vaginal Immunization Against Urinary Tract Infection." Journal of Urology 143, no. 1 (January 1990): 143–45. http://dx.doi.org/10.1016/s0022-5347(17)39898-1.

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Uehling, David T., Lori J. James, Walter J. Hopkins, and Edward Balish. "Immunization Against Urinary Tract Infection with a Multi-Valent Vaginal Vaccine." Journal of Urology 146, no. 1 (July 1991): 223–26. http://dx.doi.org/10.1016/s0022-5347(17)37756-x.

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Mulero-Marchese, R. D., K. J. Blank, and T. G. Sieck. "Genetic Basis for Protection against Experimental Vaginal Candidiasis by Peripheral Immunization." Journal of Infectious Diseases 178, no. 1 (July 1, 1998): 227–34. http://dx.doi.org/10.1086/515602.

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Gupta, Soumi, Ramesh Janani, Qian Bin, Paul Luciw, Catherine Greer, Silvia Perri, Harold Legg, et al. "Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles." Journal of Virology 79, no. 11 (June 1, 2005): 7135–45. http://dx.doi.org/10.1128/jvi.79.11.7135-7145.2005.

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ABSTRACT A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.m.), intranasal (i.n.), or intravaginal (IVAG) immunization with VEE/SIN-Gag and an IVAG challenge with vaccinia virus encoding HIV Gag (VV-Gag), a larger number of Gag-specific CD8+ intracellular gamma interferon-expressing cells (iIFNEC) were detected in iliac lymph nodes (ILN), which drain the vaginal/uterine mucosa (VUM), than were observed after immunizations with SIN-Gag. Moreover, a single i.n. or IVAG immunization with VEE/SIN-Gag induced a larger number of cells expressing HIV Gag in ILN, and immunizations with VEE/SIN-Gag through any route induced better protective responses than immunizations with SIN-Gag. In VUM, a larger percentage of iIFNEC expressed α4β7 or αEβ7 integrin than expressed CD62L integrin. However, in spleens (SP), a larger percentage of iIFNEC expressed α4β7 or CD62L than expressed αEβ7. Moreover, a larger percentage of iIFNEC expressed the chemokine receptor CCR5 in VUM and ILN than in SP. These results demonstrate a better induction of cellular and protective responses following immunizations with VEE/SIN-Gag than that following immunizations with SIN-Gag and also indicate a differential expression of homing and chemokine receptors on iIFNEC in mucosal effector and inductive sites versus systemic lymphoid tissues.

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Wei, S., W. Zou, T. Zhang, Y. Zhang, Z. Gong, and Y. Li. "Effects of GnRH agonist immunization on vaginal electrical resistance, FSH, LH, and ovaries in prepubertal female sheep." Czech Journal of Animal Science 58, No. 9 (August 29, 2013): 420–28. http://dx.doi.org/10.17221/6942-cjas.

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The study is aimed at the investigation of the effects of GnRH agonist (alarelin) immunization on the vaginal electrical resistance (VER) and secretion of FSH and LH in sheep. Forty-two prepubertal female sheep were assigned to six groups (n = 7). Animals in experimental groups I (EG-I), II (EG-II), and III (EG-III) were twice subcutaneously injected with 200, 300, and 400 µg of alarelin antigens, respectively. Animals in experimental groups IV (EG-IV) and V (EG-V) were four times subcutaneously injected with 200 and 300 µg of alarelin antigens, respectively. Animals in the control group (CG) were subcutaneously injected with 2.0 ml of control liquid. Serum concentrations of FSH and LH were detected using ELISA. VER was measured by the electrical resistance detector. The follicle vertical diameter, follicle transverse diameter, theca folliculi externa thickness (FET), theca folliculi interna thickness (FIT), and follicle wall thickness (FWT) were calculated through microscope images using ImagePlus software. The results showed that the serum FSH concentration in EGs started to increase on day 14 and reached peak levels on day 35, with a maximum in EG-V. Serum LH concentration in EGs decreased from day 7 and reached the minimum levels (P < 0.05) on day 21 or 28. Serum FSH in EG-III–EG-V was higher than that in EG-I (P < 0.05) and CG (P < 0.01) in days 28–60. VER decreased after injection of alarelin antigen, the values reached the minimum levels on day 28 in EG-I and EG-II, on day 35 in EG-III–EG-V (P < 0.05), respectively. In days 45–60, VER values in EG-III–EG-V were lower than those in CG (P < 0.01). Ovarian weights in EGs were higher than those in CG; the values of FET, FIT, FWT, follicle vertical diameter (FVD), and follicle transverse diameter (FTD) in EG-III and EG-V were greater than those in CG, EG-I, EG-II, and EG-IV. In conclusion, alarelin active immunization can decrease VER, induce the synthesis and secretion of FSH, and promote follicle development in prepubertal female sheep. VER had a positive correlation with serum LH, and a negative correlation with FSH.  

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Tengvall, Sara, Annika Lundqvist, Roselyn J. Eisenberg, Gary H. Cohen, and Ali M. Harandi. "Mucosal Administration of CpG Oligodeoxynucleotide Elicits Strong CC and CXC Chemokine Responses in the Vagina and Serves as a Potent Th1-Tilting Adjuvant for Recombinant gD2 Protein Vaccination against Genital Herpes." Journal of Virology 80, no. 11 (June 1, 2006): 5283–91. http://dx.doi.org/10.1128/jvi.02013-05.

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ABSTRACT Although sexually transmitted pathogens are capable of inducing pathogen-specific immune responses, vaginal administration of nonreplicating antigens elicits only weak, nondisseminating immune responses. The present study was undertaken to examine the potential of CpG-containing oligodeoxynucleotide (CpG ODN) for induction of chemokine responses in the genital tract mucosa and also as a vaginal adjuvant in combination with glycoprotein D of herpes simplex virus type 2 (HSV-2) for induction of antigen-specific immune responses. We found that a single intravaginal administration of CpG ODN in mice stimulates a rapid and potent response of CC chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES as well as of CXC chemokines MIP-2 and IP-10 in the vagina and/or the genital lymph nodes. Importantly, intravaginal vaccination with recombinant gD2 in combination with CpG ODN gave rise to a strong antigen-specific Th1-like immune response in the genital lymph nodes as well as the spleens of the vaccinated mice. Further, such an immunization scheme conferred both systemic and mucosal immunoglobulin G antibody responses as well as protection against an otherwise lethal vaginal challenge with HSV-2. These results illustrate the potential of CpG ODN for induction of potent chemokine responses in the genital tract and also as a vaginal adjuvant for generation of Th1-type mucosal and systemic immune responses towards a nonreplicating antigen derived from a sexually transmitted pathogen. These data have implications for the development of a mucosal vaccine against genital herpes and possibly other sexually transmitted diseases.

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Childers, Noel K., Keri L. Miller, Giang Tong, Juan Carlos Llarena, Terrance Greenway, J. Terry Ulrich, and Suzanne M. Michalek. "Adjuvant Activity of Monophosphoryl Lipid A for Nasal and Oral Immunization with Soluble or Liposome-Associated Antigen." Infection and Immunity 68, no. 10 (October 1, 2000): 5509–16. http://dx.doi.org/10.1128/iai.68.10.5509-5516.2000.

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ABSTRACT The effectiveness of monophosphoryl lipid A (MPL) as a mucosal adjuvant was investigated following oral or intranasal (i.n.) administration of an aqueous adjuvant formulation of MPL (MPL-AF) added to soluble antigen or liposomal antigen or incorporated into liposomal antigen membranes. Groups of BALB/c female mice were immunized with 50 to 100 μg of free or liposomal Streptococcus mutans crude glucosyltransferase (C-GTF) with or without MPL-AF added to the vaccine or incorporated into the liposomal membrane. Plasma, saliva, vaginal wash, and fecal extract samples were collected biweekly following immunization and assessed for antigen-specific antibody activity by enzyme-linked immunosorbent assay (ELISA). Mice immunized by the i.n. route had higher levels of salivary, plasma, and vaginal immunoglobulin A (IgA) anti-C-GTF responses and higher levels of plasma IgG anti-C-GTF than the orally immunized groups. A second administration of the vaccine 14 weeks after the initial immunization resulted in an anamnestic response to C-GTF resulting in 10- and 100-fold increases in saliva and plasma IgA and plasma IgG, respectively (in the i.n. immunized groups). Mice receiving a second i.n. immunization with liposomal antigen and MPL-AF had higher salivary IgA anti-C-GTF responses than mice immunized with antigen plus MPL-AF or liposomal antigen (P < 0.05). Plasma IgG anti-C-GTF activity was highest in mice immunized by the i.n. route with antigen formulations containing MPL-AF (P < 0.05). These results demonstrate the effectiveness of MPL-AF as an adjuvant for potentiating mucosal and systemic immune responses to liposomal C-GTF following i.n. immunization.

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40

Uehling, David T., Walter J. Hopkins, Edward Balish, Yina Xing, and Dennis M. Heisey. "Vaginal Mucosal Immunization for Recurrent Urinary Tract Infection: Phase II Clinical Trial." Journal of Urology 157, no. 6 (June 1997): 2049–52. http://dx.doi.org/10.1016/s0022-5347(01)64671-8.

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41

Mulero-Marchese, Rocio D., Kenneth J. Blank, and T. G. Sieck. "Strain-dependent migration of lymphocytes to the vaginal mucosa after peripheral immunization." Immunogenetics 49, no. 11-12 (September 2, 1999): 973–80. http://dx.doi.org/10.1007/s002510050581.

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42

Fitriadi, Yogi. "Case Report: Managing Dengue Fever at Home." Review of Primary Care Practice and Education (Kajian Praktik dan Pendidikan Layanan Primer) 4, no. 1 (April 13, 2021): 23. http://dx.doi.org/10.22146/rpcpe.56865.

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The patient is 6 years old male child, the patient went to the clinic with his parents, complaints of fever since three days ago. The fever goes up and down, reduce with administration of fever medication. The patient complained of nose bleeds 2 times, accompanied by headache. headache feels throbbing, felt constantly, and decreases with rest. The Complaints are not accompanied by coughs, sneeze, dyspnea, epigastric pain, nausea, vomiting, black stool and bloody urine. Patients still want to eat and drink. The patient has no history of traveling out of town in the past 2 weeks.The patient's mother has no history of high blood pressure and diabetes during pregnancy. The patient was born via vaginal delivery, the patient's body weight was 3250 grams. The patient was born in a healthy condition, received Hb0 immunization and vitamin K injection. The patient was treated with his mother after birth. Complete immunization history of patients according to age. Patients attend basic and mandatory immunization programs from the government.The patient is the only child of the marriage of the father and mother. The patient's father and mother are still alive, with a complete history of immunizations, now living together with his parents and grandparents. The patient's home is 8x15 meters, with tiled floors, walls made of walls, water sources are obtained from water drink company. Ventilation and home lighting is quite good. The house looks neat and not dirty. There was no visible tub of open water. The bathroom uses a shower.

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43

Parr, E. L., and M. B. Parr. "Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex virus type-2." Immunology 98, no. 4 (December 1999): 639–45. http://dx.doi.org/10.1046/j.1365-2567.1999.00909.x.

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44

Newell, Marie-Louise, and Catherine Peckham. "Mother-to-child transmission of hepatitis B infection." Fetal and Maternal Medicine Review 10, no. 2 (May 1998): 109–19. http://dx.doi.org/10.1017/s0965539597000247.

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Most transmission of hepatitis B virus (HBV) infection occurs around the time of delivery through contact with contaminated vaginal secretions or blood. Hence, interventions to reduce vertical transmission of HBV depend on identification of the infected woman during pregnancy so that the newborn infant exposed to infection can be given immunoglobulin immediately after birth, and a course of immunization can be started.

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Lehner, T., L. A. Bergmeier, L. Tao, C. Panagiotidi, L. S. Klavinskis, L. Hussain, R. G. Ward, N. Meyers, S. E. Adams, and A. J. Gearing. "Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates." Journal of Immunology 153, no. 4 (August 15, 1994): 1858–68. http://dx.doi.org/10.4049/jimmunol.153.4.1858.

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Abstract A s.c. route of immunization was developed in non-human primates, which targets the genitourinary-rectal associated lymphoid tissue. A vaccine consisting of rSIV gag p27, expressed as hybrid Ty virus-like particles (p27: Ty-VLP) was administered in the proximity of the internal iliac lymph nodes. Secretory IgA and IgG Abs to the p27 Ag were elicited in the vaginal, male urethral, rectal and seminal fluids, urine and serum. Two or more immunodominant B cell epitopes were identified within peptides 51-90 and 121-170 of the sequence of p27, using serum or biliary IgA and IgG Abs. CD4+ T cell proliferative responses to p27 were elicited predominantly in the targeted internal iliac, as well as the inferior mesenteric lymph nodes and the spleen, but not in the unrelated lymph nodes. These cells were then studied for helper function in p27 specific B cell Ab synthesis. Specific IgA and IgG Abs were detected in the same lymphoid tissues as those that displayed proliferative responses. However, cross-over reconstitution experiments between splenic and iliac lymph node B and CD4+ T cells suggest that the iliac B cells are essential for specific IgA Ab synthesis, whereas splenic B cells preferentially synthesize IgG Ab. The targeted lymph node (TLN) route of immunization gave comparable B cell, proliferative T cell, and Th cell responses to the vaginal, male genitourinary, and rectal mucosal routes, which were augmented by oral immunization. However, the TLN route induced urinary and seminal fluid sIgA and IgG Abs in addition to genital and rectal Abs. Generating secretory IgA and IgG Abs at the mucosal surfaces, and T and B cell immunity in the regional draining lymph nodes, spleen and circulation by TLN immunization may prevent transmission of virus through the mucosa, dissemination of the virus, and the formation of a latent reservoir of infection.

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46

Kang, Sang-Moo, and Richard W. Compans. "Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus." Journal of Virology 77, no. 6 (March 15, 2003): 3615–23. http://dx.doi.org/10.1128/jvi.77.6.3615-3623.2003.

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ABSTRACT Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-γ)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens.

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Bivas-Benita, Maytal, Liat Bar, Geoffrey O. Gillard, David R. Kaufman, Nathaniel L. Simmons, Avi-Hai Hovav, and Norman L. Letvin. "Efficient Generation of Mucosal and Systemic Antigen-Specific CD8+ T-Cell Responses following Pulmonary DNA Immunization." Journal of Virology 84, no. 11 (March 24, 2010): 5764–74. http://dx.doi.org/10.1128/jvi.02202-09.

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ABSTRACT Although mucosal CD8+ T-cell responses are important in combating mucosal infections, the generation of such immune responses by vaccination remains problematic. In the present study, we evaluated the ability of plasmid DNA to induce local and systemic antigen-specific CD8+ T-cell responses after pulmonary administration. We show that the pulmonary delivery of plasmid DNA formulated with polyethyleneimine (PEI-DNA) induced robust systemic CD8+ T-cell responses that were comparable in magnitude to those generated by intramuscular (i.m.) immunization. Most importantly, we observed that the pulmonary delivery of PEI-DNA elicited a 10-fold-greater antigen-specific CD8+ T-cell response in lungs and draining lymph nodes of mice than that of i.m. immunization. The functional evaluation of these pulmonary CD8+ T cells revealed that they produced type I cytokines, and pulmonary immunization with PEI-DNA induced lung-associated antigen-specific CD4+ T cells that produced higher levels of interleukin-2 than those induced by i.m. immunization. Pulmonary PEI-DNA immunization also induced CD8+ T-cell responses in the gut and vaginal mucosa. Finally, pulmonary, but not i.m., plasmid DNA vaccination protected mice from a lethal recombinant vaccinia virus challenge. These findings suggest that pulmonary PEI-DNA immunization might be a useful approach for immunizing against pulmonary pathogens and might also protect against infections initiated at other mucosal sites.

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48

Alpert, Michael D., Andrew R. Rahmberg, William Neidermyer, Sharon K. Ng, Angela Carville, Jeremy V. Camp, Robert L. Wilson, et al. "Envelope-Modified Single-Cycle Simian Immunodeficiency Virus Selectively Enhances Antibody Responses and Partially Protects against Repeated, Low-Dose Vaginal Challenge." Journal of Virology 84, no. 20 (August 11, 2010): 10748–64. http://dx.doi.org/10.1128/jvi.00945-10.

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ABSTRACT Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on weeks 18 and 24. Although this immunization regimen did not elicit antibodies capable of detectably neutralizing SIVmac239 or SIVmac251UCD, neutralizing antibody titers to the envelope-modified strains were selectively enhanced. Virus-specific antibodies and T cells were observed in the vaginal mucosa. After 20 weeks of repeated, low-dose vaginal challenge with SIVmac251UCD, six of eight immunized animals versus six of six naïve controls became infected. Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naïve control animals.

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Wu, Hong-Yin, Samira Abdu, Dana Stinson, and Michael W. Russell. "Generation of Female Genital Tract Antibody Responses by Local or Central (Common) Mucosal Immunization." Infection and Immunity 68, no. 10 (October 1, 2000): 5539–45. http://dx.doi.org/10.1128/iai.68.10.5539-5545.2000.

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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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Challacombe, S. J., D. Rahman, and D. T. O'Hagan. "Salivary, gut, vaginal and nasal antibody responses after oral immunization with biodegradable microparticles." Vaccine 15, no. 2 (February 1997): 169–75. http://dx.doi.org/10.1016/s0264-410x(96)00159-4.

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