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Haemophilus ducreyi causes genital ulceration (chancroid), a sexually transmitted infection and still an important factor which contributes to the spread of HIV in developing countries. The bacterium produces a cytolethal distending toxin (HdCDT) causing cell cycle arrest and apoptosis/necrosis of human cells and contributes to the aggravation of ulcers. The aim of the study was to induce toxin-neutralizing antibodies in the genital tract of mice. Repeated subcutaneous (sc) immunisations with 5-10microg active HdCDT induced low levels of serum anti-HdCDT IgG without neutralizing capacity. High levels of specific IgG1 antibodies in serum and genital tract were generated after sc immunisations with 10microg formaldehyde detoxified HdCDT toxoid alone and the addition of aluminium salts or RIBI (based on the lipid A moiety) as adjuvant further increased the level of serum antibodies. A high correlation was found between elevated levels of anti-HdCDT IgG in sera, the level of neutralizing activity and the antibody level in genital tract (r=0.8). Thus, induction of high antibody levels specific to HdCDT in the genital tissue can be achieved by parenteral immunisation with the toxoid. The HdCDT toxoid can be considered as a candidate component in vaccine against chancroid.

A vaccine against heterosexual transmission by human immunodeficiency virus (HIV) should generate cytotoxic and antibody responses in the female genital tract and in extra-genital organs. We report that sublingual immunization with HIV-1 gp41 and a reverse transcriptase polypeptide coupled to the cholera toxin B subunit (CTB) induced gp41-specific IgA antibodies and antibody-secreting cells, as well as reverse transcriptase-specific CD8 T cells in the genital mucosa, contrary to intradermal immunization. Conjugation of the reverse transcriptase peptide to CTB favored its cross-presentation by human dendritic cells to a T cell line from an HIV(+) patient. Sublingual vaccination could represent a promising vaccine strategy against heterosexual transmission of HIV-1., (Copyright 2010 Elsevier Ltd. All rights reserved.)

We have shown previously that vaccination with recombinant chlamydial protease-like activity factor (rCPAF) plus interleukin-12 as an adjuvant induces robust protective immunity against primary genital Chlamydia muridarum challenge in mice. Since CPAF is a protease, we compared the effects of enzymatically active and inactive (heat denatured) rCPAF to determine whether proteolytic activity is expendable for the induction of protective immunity against chlamydial challenge. Active, but not inactive, rCPAF immunization induced high levels of anti-active CPAF antibody, whereas both induced robust splenic CPAF-specific IFN-gamma production. Vaccination with active or inactive rCPAF induced enhanced vaginal chlamydial clearance as early as day 6 with complete resolution of infection by day 18, compared to day 30 in mock-vaccinated and challenged animals. Importantly, significant and comparable reductions in oviduct pathology were observed in active and inactive rCPAF-vaccinated mice compared to mock-vaccinated animals. Thus, rCPAF induced anti-chlamydial immunity is largely independent of enzymatic activity and secondary or higher order protein conformation., (Copyright 2009 Elsevier Ltd. All rights reserved.)

AdC6gag37, an E1-deleted adenovirus recombinant derived from the chimpanzee adenovirus serotype 6 expressing a codon-optimized truncated form of gag of HIV-1, was tested for induction of transgene-specific CD8+ T cell responses upon intranasal or intravaginal immunization of mice. Administration of AdC6gag37 induced gag-specific CD8+ T cells at systemic and mucosal sites. Frequencies of gag-specific CD8+ T cells elicited in the genital tract by intravaginal or intranasal immunizations were substantially increased by intranasal priming followed by intravaginal boosting with the same vector. Additionally, intravaginal immunization with AdC6gag37 increased the amount of gammadelta T cells that could be detected in genital tract.

The female genital tract is an important site for numerous pathogens entry. Local immunization, generating specific mucosal IgA and systemic IgG, represents an interesting alternative immunization pathway. However, such a vaccine strategy needs mucosal adjuvants to obtain the best immune response. Considering that the immunization process is mainly dependent on the capture and on the transport of the antigen by Langerhans cells, we evaluated potential adjuvant molecules by analysing their effects on the CCL20 secretion by endocervical and exocervical/vaginal epithelial cells as well as on dendritic cell and Langerhans cell maturation. We demonstrated that DC-Chol and Zymosan are the most efficient mucosal candidate immunoadjuvants that generate a strong increase of CCL20 secretion by the two epithelial cell lines and the maturation of dendritic and Langerhans cells, respectively.

Exclusion of infectious agents from mucosal surfaces of the reproductive tract is a key objective of microbicides and mucosal vaccines. With mucosal antibodies as a common mechanism of exclusion, parallel development of passive and active immunization strategies is an opportunity to determine and achieve protective antibody concentrations in the female reproductive tract. Recognizing that access to sexual and reproductive health products will require low-cost and high-capacity production technologies, the emerging tools of plant biotechnology for complex biopharmaceutical production are crucial. Unfortunately, few preclinical or clinical studies have been completed to date with plant-derived agents intended for reproductive health.

Previously, we demonstrated that intranasal (i.n.) but not intraperitoneal (i.p.) immunization with a recombinant adenovirus vector expressing glycoprotein B (gB) of herpes simplex virus type 1 (HSV-1) induced mucosal immune responses and conveyed long-term protection to mice against an i.n. challenge with heterologous HSV-2. We now show that i.n. immunization of female mice with this same vector, AdgB8, provides secretory and serum-derived humoral immune responses in the genital tract. Intranasal immunization induced anti-HSVgB IgA and IgG in vaginal washes of mice, whereas i.p. immunization only induced IgG, which appeared to be serum-derived. Interestingly, intravaginal (ivag) immunization with AdgB8 resulted in little or no anti-HSVgB IgA and only low levels of specific IgG in vaginal washes. All three routes of inoculation induced gB-specific serum IgG and IgA; however, i.n. immunized mice demonstrated the highest level of serum anti-HSVgB IgA. Additionally, ivag boosting with AdgB8 did not significantly alter the serum or vaginal wash antibody responses in i.n. or i.p. immunized mice. The IgG to IgA ratios of gB-specific and total antibody titres in the serum and vaginal washes of i.n. immunized mice indicated that the IgA in the vaginal washes was likely to be secretory. Furthermore, the titres of anti-HSVgB IgA relative to total IgA were higher in vaginal washes than sera, suggesting that the gB-specific vaginal wash IgA present in i.n. immunized mice was locally produced.