Immunoglobulin to zona pellucida 3 mediates ovarian damage and infertility after contraceptive vaccination in mice

Lloyd, Megan; Papadimitriou, John; O’Leary, Seán; Robertson, Sarah A.; Shellam, Geoffrey

doi:10.1016/j.jaut.2010.03.002

Cited by 27 publications

(21 citation statements)

References 31 publications

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“…Calongos et al (40) and Lloyd et al (16) found that anti-ZP Abs were detrimental to normal folliculogenesis and oocyte development. Anti-ZP Abs may give rise to follicle loss and premature ovarian failure because they impair zona pellucida formation in developing follicles and formation of gap junctions between the oocyte and granulosa cells (16,40). Some reports suggested that anti-ZP Abs may induce infertility of immunized mice via two mechanisms, one disrupting ZP formation and oocyte development and the other blocking sperm-oocyte binding and oocyte fertilization.…”

Section: Discussionmentioning

confidence: 99%

“…Some reports suggested that anti-ZP Abs may induce infertility of immunized mice via two mechanisms, one disrupting ZP formation and oocyte development and the other blocking sperm-oocyte binding and oocyte fertilization. The degree to which these two mechanisms each bear responsibility for infertility may rely on the Ab titer and the interval since the beginning of the response (16). Our results showed that chi-(pcD- Lzp3 +pcD- mIL-33 ) co-immunization induced significantly higher levels of Abs in infertile mice than in fertile mice, suggesting that the infertility may be due to the Abs blocking sperm-oocyte binding.…”

Section: Discussionmentioning

confidence: 99%

“…Except for the direct effects of ZP3 Abs blocking the sperm binding site, some studies showed that ovarian pathological features characterized by depletion of primordial follicles and loss of follicles might cause the infertility induced by ZP3 protein vaccination (7,13). Accumulated evidence indicates that both T cell and Ab-mediated reactions could cause ovarian pathology (14-16). For humans, a safe immunocontraceptive vaccine should not induce ovarian pathology.…”

Section: Introductionmentioning

confidence: 99%

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Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route

Kadir

Zhang

2013

Braz J Med Biol Res

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It has been shown that cytokines can act as molecular adjuvant to enhance the immune response induced by DNA vaccines, but it is unknown whether interleukin 33 (IL-33) can enhance the immunocontraceptive effect induced by DNA vaccines. In the present study, we explored the effects of murine IL-33 on infertility induced by Lagurus lagurus zona pellucida 3 (Lzp3) contraceptive DNA vaccine administered by the mucosal route. Plasmid pcD-Lzp3 and plasmid pcD-mIL-33 were encapsulated with chitosan to generate the nanoparticle chi-(pcD-Lzp3+pcD-mIL-33) as the DNA vaccine. Sixty female ICR mice, divided into 5 groups (n=12/group), were intranasally immunized on days 0, 14, 28, and 42. After intranasal immunization, the anti-LZP3-specific IgG in serum and IgA in vaginal secretions and feces were determined by ELISA. The results showed that chi-(pcD-Lzp3+pcD-mIL-33) co-immunization induced the highest levels of serum IgG, secreted mucosal IgA, and T cell proliferation. Importantly, mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) had the lowest birth rate and mean litter size, which correlated with high levels of antibodies. Ovaries from infertile female mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) showed abnormal development of ovarian follicles, indicated by atretic follicles and loss of oocytes. Our results demonstrated that intranasal delivery of the molecular adjuvant mIL-33 with chi-pcD-Lzp3 significantly increased infertility by enhancing both systemic and mucosal immune responses. Therefore, chi-(pcD-Lzp3+pcD-mIL-33) co-immunization could be a strategy for controlling the population of wild animal pests.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route

Kadir

Zhang

2013

Braz J Med Biol Res

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“…MCMV was first tested for its ability to induce immunologic contraception using a recombinant virus expressing zona pellucida 3, an ovary antigen, in an attempt to control mouse populations in Australia [89]. Interestingly, this vaccine did not work by inducing zona pellucida 3-specific T cells, but rather antibodies that could sterilize the infected mice [90]. In contrast, infection with recombinant MCMVs expressing the MHC class I restricted viral epitopes from influenza nucleoprotein or LCMV-glycoprotein induced protection against Vaccinia virus expressing nucleoprotein or glycoprotein respectively that correlated with T-cell numbers in the vaccinated mice [86].…”

Section: As a Vaccine Vectormentioning

confidence: 99%

Cytomegalovirus and Immunotherapy: Opportunistic Pathogen, Novel Target for Cancer and a Promising Vaccine Vector

2016

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Cytomegalovirus (CMV) is a β-herpesvirus that infects most people in the world and is almost always asymptomatic in the healthy host. However, CMV persists for life, requiring continuous immune surveillance to prevent disease and thus, CMV is a frequent complication in immune compromised patients. Many groups have been exploring the potential for adoptive T-cell therapies to control CMV reactivation as well as the progression of solid tumors harboring CMV. In addition, CMV itself is being explored as a vaccine vector for eliciting potent T-cell responses. This review will discuss key features of the basic biology of CMV-specific T cells as well as highlighting unanswered questions and ongoing work in the development of T-cell-based immunotherapies to target CMV.

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“…Intra cytoplasmic sperm injection (ICSI) is recommended option for IVF therapy of women with anti-ZP autoantibodies (Mardesic et al, 2000). Anti-ZP autoantibodies may induce autoimmune-mediated ovarian damage with follicular depletion and fertility suppression due to impaired ZP formation (Lloyd et al, 2010) and disruption of the gap junctions between the oocyte and granulosa cells, damaging the bidirectional communication necessary for normal folliculogenesis (Calongos et al, 2009). …”

Section: Anti-ovarian Antibodies and Infertilitymentioning

confidence: 99%

Ovarian Biomarkers in Infertility

Vangelov¹,

Dineva²,

Todorova³

et al. 2012

Trends in Immunolabelled and Related Techniques

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Immunoglobulin to zona pellucida 3 mediates ovarian damage and infertility after contraceptive vaccination in mice

Cited by 27 publications

References 31 publications

Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route

Molecular adjuvant interleukin-33 enhances the antifertility effect of Lagurus lagurus zona pellucida 3 DNA vaccine administered by the mucosal route

Cytomegalovirus and Immunotherapy: Opportunistic Pathogen, Novel Target for Cancer and a Promising Vaccine Vector

Ovarian Biomarkers in Infertility

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