Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo

Khan, Md. Abu Hadi Noor Ali; Ferro, Valerie A.; Koyama, Shinsuke; Kinugasa, Yukiko; Song, Mihyon; Ogita, Kazuhide; Tsutsui, Tateki; Murata, Yuji; Kimura, Tadashi

doi:10.1016/j.vaccine.2007.01.089

Cited by 24 publications

(30 citation statements)

References 31 publications

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“…The dose of GnRH DNA vaccine having two copies of GnRH (50 μg/100 μl) in this study was lower than that of GnRH DNA vaccine having five copies of GnRH (100 μg/100 μl) in Khan's study (Khan et al. ), indicating that 50 μg/100 μl of two copies GnRH DNA vaccine be enough to induce GnRH antibody response. Yet, the antibody response of GnRH DNA vaccine was relatively weak.…”

Section: Discussioncontrasting

confidence: 60%

“…Previous research has shown that GnRH can be used as a target for developing DNA immunocastration vaccine (Khan et al. , ). However, the GnRH is an incomplete antigen; its immunogenicity is weak; its vaccine use needs to be improved by coupling with a large carrier molecule to enhance the immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, mice vaccinated with GnRH vaccine showed high anti‐GnRH antibodies in plasma, this might block the function of GnRH, and thus, lead to the impairment of sexual organs and suppression of spermatogenesis (Khan et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…The use of DNA vaccines (Khan et al. , ) is one successful strategy for immunocastration, which do not need the purification of protein antigens and are considered to be safe, convenient and cost effective (Robertson and Griffiths ; Redding and Weiner ). The GnRH DNA immunocastration vaccine developed by Khan et al.…”

Section: Introductionmentioning

confidence: 99%

“…The GnRH DNA immunocastration vaccine developed by Khan et al. (, ) used a pcDNA3.1 vector which contains ampicillin resistance gene; it is liable to cause allergic responses (Sachs et al. ).…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis B Surface Antigen S Gene is an Effective Carrier Molecule for Developing GnRH DNA Immunocastration Vaccine in Mice

Han

Liu

et al. 2016

Reprod Domestic Animals

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Relatively molecular mass of GnRH antigens is small and hence needs to couple to a large carrier molecule to enhance its immunogenicity. This study investigated whether hepatitis B surface antigen S (HBsAg-S) gene can be used as an effective carrier molecule for developing GnRH DNA immunocastration vaccine. Two copies of human GnRH gene were fused with HBsAg-S gene for constructing a recombinant plasmid pVAX-HBsAg-S-2GnRH that coded for 27 kDa target fusion protein. Ten male mice were divided into two equal groups, treatment and control. The vaccine (50 μg/mice) prepared in saline solution was injected into male mice at weeks 0, 1, 2, 4 and 7 of the experiment. Vaccine's efficacy was evaluated in terms of GnRH-specific IgG antibody response, plasma testosterone levels, testicular weight and extent of the testicular tissue damage. The specific anti-GnRH antibody titre in vaccinated animals was significantly higher than in controls in only 4th week of immunization (p < 0.05). In addition, vaccinated animals showed lower testicular weight than those of the controls (p < 0.05). Spermatogenesis in seminiferous tubules in vaccinated animals was suppressed. In conclusion, in this study, the engineered plasmid to be used as a GnRH DNA vaccine induced antibody response and suppressed spermatogenesis in mice. This suggests that HBsAg-S gene can be an effective carrier molecule for developing GnRH DNA immunocastration vaccine when relatively molecular mass of the aimed antigens is small.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hepatitis B Surface Antigen S Gene is an Effective Carrier Molecule for Developing GnRH DNA Immunocastration Vaccine in Mice

Han

Liu

et al. 2016

Reprod Domestic Animals

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Detection of antibodies against customized epitope: use of a coating antigen employing VEGF as fusion partner

Wang

Zhou

Zhu

et al. 2014

Appl Microbiol Biotechnol

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Diagnosis of many infectious, autoimmune diseases and cancers depends on the detection of specific antibodies against peptide epitope by enzyme-linked immunosorbent assay (ELISA). However, small peptides are difficult to be coated on the plate surfaces. In this study, we selected GnRH as a model hapten to evaluate whether VEGF121 would be suitable as an irrelevant hapten-carrier to develop a universal platform for specific antibodies detection. Firstly, GnRH was fused to the C terminus of VEGF121 and the resultant fusion protein VEGF-GnRH expressed effectively as inclusion bodies in Escherichia coli. Thereafter, VEGF-GnRH was easily purified to near homogeneity with a yield of about 235 mg from 2.1 L induced culture. At last, VEGF-GnRH was used to perform ELISA and western blot, and our results suggested that VEGF-GnRH was capable of detecting anti-GnRH antibodies in sera both qualitatively and quantitatively. Indeed, previous studies of our laboratory had demonstrated that other fusion proteins such as VEGF-Aβ10, VEGF-GRP, VEGF-CETPC, and VEGF-βhCGCTP37 were able to detect their corresponding antibodies specifically. Therefore, VEGF121 may be a suitable irrelevant fusion partner of important diagnostic peptide markers. Our works would shed some light on the development of a universal platform for detection of specific antibodies.

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DNA Vaccine Targeting Gonadotropin-Releasing Hormone Receptor and Its Application in Animal Contraception

et al. 2018

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Overpopulation of free-roaming and wildlife animals negatively affects economy and public health in many parts of the world. Contraceptive vaccines are viewed as a valuable option for reducing numbers of unwanted animals. This study develops vaccines for potential use in animal contraception exploiting a DNA platform. Objectives of the study were to generate DNA constructs directed against gonadotropin-releasing hormone receptor (GnRHR), a crucial molecular player in animal reproduction, and characterize them for ability to promote immune responses and suppression of reproductive parameters in vivo. DNA constructs were created to encode for a recombinant protein composed of two domains: GnRHR, the target antigen, and ubiquitin (Ub), a support protein. Ub-GnRHR constructs administered intramuscularly or intradermally or containing different promoters were compared. CMV and EF1α promoters were shown to be superior to CAG. In fertility trials, mice immunized intradermally with Ub-GnRHR construct driven by EF1α had a significantly lower number of fetuses. Importantly, the impaired fertility was achieved with a single DNA immunization and without the use of adjuvants. The study demonstrated for the first time that targeting the GnRH receptor with DNA-based vaccines could be a viable option for animal contraception.

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Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo

Cited by 24 publications

References 31 publications

Hepatitis B Surface Antigen S Gene is an Effective Carrier Molecule for Developing GnRH DNA Immunocastration Vaccine in Mice

Hepatitis B Surface Antigen S Gene is an Effective Carrier Molecule for Developing GnRH DNA Immunocastration Vaccine in Mice

Detection of antibodies against customized epitope: use of a coating antigen employing VEGF as fusion partner

DNA Vaccine Targeting Gonadotropin-Releasing Hormone Receptor and Its Application in Animal Contraception

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