Antibodies against spermatozoal surface—membrane antigens in female infertility

Ingerslev, Hans Jakob

doi:10.3109/00016348109156938

Cited by 24 publications

(11 citation statements)

References 175 publications

(58 reference statements)

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“…Reports of auto‐ or iso‐antibodies against sperm proteins in men and women with idiopathic infertility (Ingerslev, ; Francavilla et al, ) suggest that sperm components are ideal contraceptive vaccine candidates. Indeed, the contraceptive potential of several sperm proteins—such as Lactate dehydrogenase‐C 4 , PH20, Fertilin (PH30), Sp10, Sp17, Sp56, Fertilization Antigen‐1, Izumo, YLP 12 dodecamer peptide, CatSper1, Eppin, 80‐kDa Human sperm antigen, Proacrosin, and Cystein‐rich secretory protein‐1 (CRISP1)—were previously shown to provide variable efficacy in different animal models (reviewed by Gupta et al, ).…”

Section: Discussionmentioning

confidence: 99%

Novel Sperm and Gonadotropin‐releasing Hormone‐based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co‐immunization of Male and Female Mice

Minhas

Shrestha

Wadhwa

et al. 2016

Molecular Reproduction Devel

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Improvements in long-term female contraception can be achieved by vaccinating with sperm-derived proteins. Here, recombinant proteins comprising either (i) N- (amino acid residues 1-80) or C- (amino acid residues 76-126) terminal fragments of mouse sperm protein 17 (Sp17) fused to the promiscuous T non-B cell epitope of tetanus toxoid (TT), amino acid residues 830-844 followed by di-lysine linker (KK) (TT-KK-Sp17 or TT-KK-Sp17 , respectively) or (ii) mouse equatorin (amino acid residues 21-185) fused to the T non-B cell epitope of bovine RNase (amino acid residues 94-104) were expressed in Escherichia coli. Immunization of female FVB/J mice, using alum as an adjuvant, led to the generation of high antibody titers against the above proteins. Antibodies against both N- and C-terminal fragments of Sp17 reacted with the entire capacitated mouse spermatozoa, whereas those against equatorin reacted exclusively with the equatorial region. Despite the reactivity of all immune sera, only sera from mice immunized with TT-KK-Sp17 and TT-KK-Sp17 significantly reduced mouse in vitro fertilization. Mating studies of the immunized females with un-immunized male mice revealed the highest infertility in the TT-KK-Sp17 -immunized group. In an attempt to further boost the immune response, the C-terminal fragment of Sp17 was expressed as fusion protein with a tandem repeat of gonadotropin-releasing hormone (GnRH) (Sp17 -GnRH ). Immunization of both male and female mice with Sp17 -GnRH led to higher contraceptive efficacy compared to mice immunized with TT-KK-Sp17 . Interestingly, mating studies wherein partners were both immunized with Sp17 -GnRH showed a complete failure of female mice to conceive. Thus, immunization of both males and females with Sp17 -GnRH has the potential to increase contraceptive efficacy. Mol. Reprod. Dev. 83: 1048-1059, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Novel Sperm and Gonadotropin‐releasing Hormone‐based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co‐immunization of Male and Female Mice

Minhas

Shrestha

Wadhwa

et al. 2016

Molecular Reproduction Devel

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“…Initial immunization studies in animals as well as humans with either sperm or its extracts resulted in the production of antisperm antibodies that led to infertility [20,21]. These studies are supplemented by nature's experiment where the presence of antisperm antibodies in women and men is associated with idiopathic infertility [22,23]. Encouraged by these observations, several laboratories across the world initiated programs to identify and characterize sperm-specific antigens that could fulfill the criteria to be candidate antigens for the development of contraceptive vaccines.…”

Section: Contraceptive Vaccines Based On Spermatozoa-specific Antigensmentioning

confidence: 99%

Vaccines for immunological control of fertility

Gupta

Bansal

2009

Reprod Medicine & Biology

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Vaccines have been proposed as one of the strategies for population control. Immunocontraceptive vaccines can be designed to inhibit: (1) production of gametes (sperm and egg); (2) functions of gametes, leading to blocking of fertilization; and (3) gamete outcome (pregnancy). Immunization with gonadotropin-releasing hormone coupled to different carriers has shown curtailment in the production of sperm with concomitant infertility in various species. Immunization of nonhuman primates and men with ovine follicle stimulating hormone has also resulted in reduced sperm output. Various spermatozoa-specific proteins such as FA1, PH-20, LDH-C, SP-10, SP-17, sp56, SPAG9, and Izumo have been proposed as candidate antigens to develop contraceptive vaccines, which have shown efficacy in inhibiting fertility in different animal models. Immunization with zona pellucida glycoproteins-based immunogens also results in curtailment of fertility in a variety of species. However, ways to overcome the observed oophoritis associated with zona proteins immunization have yet to be discovered, a necessary step before their proposal for control of human population. Nonetheless, this is a very promising approach to control wildlife animal population. Phase II clinical trials of β-human chorionic gonadotropin-based vaccine in women have established the proof of principle that it is possible to inhibit fertility without any untoward side-effects by vaccination. Further scientific inputs are required to increase the efficacy of contraceptive vaccines and establish their safety beyond doubt, before they can become applicable for control of fertility in humans.

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“…In women, several clinical studies have revealed that antibodies against sperm are frequently associated with otherwise unexplained infertility [6]. These experiments of nature documenting that immunocontraception is feasible in humans prompted several groups to identify, characterize and evaluate the immunocontraceptive potential of spermatozoa-specific antigens.…”

Section: Sperm-specific Antigensmentioning

confidence: 99%

Immunocontraceptive Approaches in Females

Gupta¹,

Chakravarty²,

Kadunganattil³

2005

Chemical Immunology and Allergy, 2005

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In the female reproductive system, there are multiple points, where immunointerception is feasible. Among these, the most promising are those that interfere immunologically at the level of sperm-egg interaction or neutralize human chorionic gonadotropin (hCG), which is required for the establishment and maintenance of pregnancy. Immunization studies in various animal models including non-human primates with zona pellucida (ZP) glycoproteins have demonstrated curtailment of fertility. To circumvent the ovarian pathology often observed following immunization with ZP glycoproteins, synthetic peptides devoid of 'oophoritogenic' T cell epitopes as immunogens have been proposed. Though of utility for controlling wildlife populations, its application in humans will have to wait till the safety of ZP glycoprotein vaccine is established beyond doubt. Clinical trials in women have established that immunocontraceptive vaccine based on Beta-subunit of hCG inhibits fertility. To make it a practical proposition, novel strategies have to be adopted to increase its immunogenicity so that 'contraceptive' antibody titers are achieved in near to 100% recipients.

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Antibodies against spermatozoal surface—membrane antigens in female infertility

Cited by 24 publications

References 175 publications

Novel Sperm and Gonadotropin‐releasing Hormone‐based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co‐immunization of Male and Female Mice

Novel Sperm and Gonadotropin‐releasing Hormone‐based Recombinant Fusion Protein: Achievement of 100% Contraceptive Efficacy by Co‐immunization of Male and Female Mice

Vaccines for immunological control of fertility

Immunocontraceptive Approaches in Females

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