Abstract
| Language | English |
|---|---|
| Pages | 3544-3553 |
| Number of pages | 10 |
| Journal | Vaccine |
| Volume | 25 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - 4 May 2007 |
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Keywords
- in vivo fertility
- anti-GnRH-I antibody
- GnRH-I vaccine
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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. / Khan, M.A.H.; Ferro, V.A.; Koyama, M.; Kinugasa, Y.; Song, M.; Ogita, K.; Murata, Y.; Kimura, T.
In: Vaccine, Vol. 25, No. 18, 04.05.2007, p. 3544-3553.Research output: Contribution to journal › Article
TY - JOUR
T1 - Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and t-helper epitopes suppresses fertility in vivo
AU - Khan, M.A.H.
AU - Ferro, V.A.
AU - Koyama, M.
AU - Kinugasa, Y.
AU - Song, M.
AU - Ogita, K.
AU - Murata, Y.
AU - Kimura, T.
PY - 2007/5/4
Y1 - 2007/5/4
N2 - Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.
AB - Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.
KW - in vivo fertility
KW - anti-GnRH-I antibody
KW - GnRH-I vaccine
U2 - 10.1016/j.vaccine.2007.01.089
DO - 10.1016/j.vaccine.2007.01.089
M3 - Article
VL - 25
SP - 3544
EP - 3553
JO - Vaccine
T2 - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 18
ER -