Assessment of contraceptive vaccines based on recombinant mouse sperm protein PH20

Pest Animal Control Cooperative Research Centre, CSIRO Sustainable Ecosystems, GPO Box 284, Canberra, ACT 2601, Australia.
Reproduction (Cambridge, England) (Impact Factor: 3.17). 04/2004; 127(3):325-34. DOI: 10.1530/rep.1.00016
Source: PubMed


Mouse PH20 (mPH20), the mouse homologue to guinea pig hyaluronidase protein PH20 (gpPH20), was used to produce contraceptive vaccines that target both sexes of mice. Previously, immunization with a female gamete antigen (the zona pellucida subunit 3 protein) delivered in a recombinant murine cytomegalovirus (MCMV), or as a purified recombinant protein, has been shown to induce infertility in female mice. There is evidence, however, that sperm protein antigens could provide broader contraceptive coverage by affecting both males and females, and the most promising has been gpPH20 when tested in a guinea pig model. Mice were therefore either inoculated with a recombinant MCMV expressing mPH20 or immunized directly with purified recombinant mPH20 protein fused to maltose-binding protein. Mice treated with either vaccine formulation developed serum antibodies that cross-reacted to a protein band of 55 kDa corresponding to mPH20 in Western blots of mouse sperm. However, there was no significant reduction in the fertility of males or females compared with control animals with either formulation. We conclude from our data that recombinant mPH20 is not a useful antigen for inclusion in immunocontraceptive vaccines that target mice.

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Available from: Clive Sweet, Oct 08, 2015
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    • "In P1/P2 immunized groups, there were no significant correlations between reduction in fertility and titers of circulating antibodies. The induced infertility was reversible and the result was in accord with other findings (Lea et al., 1998; Naz and Zhu, 1998; Gaudreault et al., 2002; Hardy et al., 2004b). The inhibition of rates of fertilization in vitro using cumulus intact oocytes incubated with the antibodies against mESP fragments P1 or P2 was higher than that of fertility in vivo. "
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    ABSTRACT: To investigate antifertility characteristics of the equatorial segment protein (ESP) and its potential immunocontraceptive effect, three partially overlapping cDNA fragments P1/P2/P3, together covering the entire mouse ESP, were cloned, expressed, and purified. The roles of P1/P2/P3 in fertility were investigated through in vitro fertilization and mouse mating test. Antibodies against P1/P2 significantly reduced the rates of fertilization in vitro in the zona-intact experiments. Coincubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of antibodies against P1/P2 also inhibited sperm-oolemma binding and fusion, while anti-P3 antibody virtually had no effect on in vitro fertilization at the same concentration. Immunization of female BALB/c mice with N-terminal of mouse ESP (recombinant P1 and P2) resulted in a significant decrease in the fertility rate as well as the litter size. Double immunofluorescence staining showed that mouse ESP protein was localized to the equatorial segment of acrosome of mouse sperm, and was exposed and surface-accessible after acrosome reaction. Mouse ESP was also demonstrated to have complementary binding sites on the mouse egg plasma membrane by indirect immunofluorescence assay. These findings suggest that the N-terminal of mouse ESP could play an important role in fertility and might be a vaccine candidate for contraception.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 01/2010; 293(1):171-81. DOI:10.1002/ar.21032 · 1.54 Impact Factor
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    • "Left lane, prestained protein molecular weight standards (Benchmark, Gibco-BRL, Rockville, MD, USA). immunocontraceptive vaccinogen demonstrated fertility suppression in the female guinea pigs (Primakoff et al., 1988), which, however, failed in mice and rabbit fertility trials (Pomering et al., 2002; Hardy et al., 2004b). Similarly, LDH- C4 showed promising results in mouse but failed to show any contraceptive effect in non-human primates by an independent fertility trial in macaques (Tollner et al., 2002). "
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    Human Reproduction 12/2006; 21(11):2894-900. DOI:10.1093/humrep/del068 · 4.57 Impact Factor
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    • "Antigens other than mZP3 have so far failed to cause infertility in mice when delivered using recombinant MCMV. These include sperm protein PH20 (Hardy et al., 2004a), pig ZPC, germ cell factor, oviduct glycoprotein and four synthetic multi-antigen peptide constructs (A. Redwood, unpublished results). "
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