Brazilian spotted fever prevention through a nonlethal capybara population control strategy

Abstract INTRODUCTION: Brazilian spotted fever (BSF), a lethal tick-borne Rickettsioses (2000 - 2018 >600 human deaths) involving synanthropic capybara as host. METHODS: We introduced an alternative to mitigate human-capybara conflicts and epidemiologic concerns of BSF. Complex aspects like transmission dynamics, risk areas, host mobility, and birth rate control, were considered to develop a prevention strategy using an anti-GnRH vaccine. RESULTS: The propositioned immunocontraceptive potentially remove and prevent the spread of BSF from endemic areas. CONCLUSIONS: We propose the anti-GnRH vaccine as a BSF prevention strategy based on these favorable results.

Evaluation of infertility efficacy of the E. coli expressed STF2-GnRH vaccine in male cats

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.

Evaluation of immunocontraceptive vaccine composed of gonadotropin-releasing hormone conjugated with granulocyte-macrophage colony-stimulating factor in male rats

Surgical castration performed to reduce male-associated problems results in pain and microbial infections in male animals. Therefore, immunocontraception, which is mediated by the animal's own antibodies against reproductive hormones, has been recommended as an alternative to surgical castration when considering the animal's welfare. In this study, a new immunocontraceptive vaccine composed of six tandem copies of gonadotropin-releasing hormone (GnRH) fused to rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed, and its efficacy was evaluated in male rats. Three different doses (10, 50, and 100 µg) of recombinant GM-CSF–GnRH protein were injected three times at intervals of two weeks into male rats. The rats vaccinated with three doses of GM-CSF–GnRH produced a significantly higher level of antibodies against GnRH than that in the negative control rats. Severe atrophy of gonads was observed in rats vaccinated with three doses of GM-CSF–GnRH but not in the negative control rats. The results reveal that the new GnRH vaccine conjugated with rat GM-CSF induces efficient immunocontraception in male rats. This formulation of the immunocontraceptive vaccine would be applicable to both domestic and pet male animals.

Progress in researches on male immunocontraception / 中华男科学杂志

The ideal goal of male immunocontraception is to develop a safe, effective, convenient, acceptable and reversible contraceptive vaccine. Current studies mainly focus on screening the most suitable target antigens from reproductive hormones and sperm functional proteins for the development of immuno contraceptive vaccines. The vaccine targeting reproductive hormones has not been widely used due to its different degrees of side effects and complicated operation. Recent studies show the practicability and applicability of the immuno contraceptive vaccine targeting sperm specific antigens, but its development is confronted with many challenges, such as how to select appropriate target antigens, how to enhance the immunogenicity of the vaccine, how to choose appropriate drug-delivery ways, how to reduce its side effects, and how to decrease its cost.

The antibody against a nuclear autoantigenic sperm protein can result in reproductive failure / 亚洲男科学杂志(英文版)

To study whether the antibody against the testis form of the nuclear autoantigenic sperm protein (tNASP) could result in reproductive failure, we successfully cloned and expressed a 339-bp cDNA fragment of mouse tNASP (mtNASP). Using mouse as a model, recombinant mtNASP (rmtNASP) and a synthetic peptide, human tNASP(393-408) (htNASP(393-408)), were investigated for their antifertility effect. Active immunization with rmtNASP or the synthesized peptide raised high antibody titers in the immunized mice. Sperm-egg binding and fusion assay were carried out in 8-10-week-old BALB/c mice. Sperm-egg binding and in vitro fertilization of mouse oocytes were inhibited by co-incubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of varying concentrations of the antisera against rmtNASP. There was a significant antifertility effect in animals immunized with rmtNASP or the synthesized peptide. The effect on fertility in the mice immunized with the synthesized peptide was reversible. Our data indicate that active immunization with rmtNASP antigen may induce a strong antibody response that causes an inhibition of fertility.

Detection of anti-Sp17 antibodies in infertile patients' serum and its clinical significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To test anti-Sp17 antibodies in the serum of AsAb positive infertile patients, to investigate the proportion of anti-Spl7 antibodies in AsAb and their potential application to the serologic diagnosis of immune infertility and immunocontraception.</p><p><b>METHODS</b>With human recombinant Sp17 as the antigen, the ELISA method was used to detect the positive rate, antibody titre and content of anti-Sp17 antibodies in the AsAb positive serum.</p><p><b>RESULTS</b>The positive rate of anti-Sp17 antibodies in the AsAb positive serum was 56.5%, with no significant difference in the gender aspect. The percentage of anti-Sp17 antibodies in AsAb was (10.09 +/-7.45) %, with statistical significance (P <0.05).</p><p><b>CONCLUSION</b>Sp17 is an important sperm antigen. Anti-Sp17 antibodies in the serum can be taken as auxiliary diagnostic index of infertility, and Sp17 is shown to be a potential candidate immunocontraception vaccine.</p>

Induction of castration by immunization of male dogs with recombinant gonadotropin-releasing hormone (GnRH)-canine distemper virus (CDV) T helper cell epitope p35

Immunocastration is a considerable alternative to a surgical castration method especially in male animal species for alleviating unwanted male behaviors and characteristics. Induction of high titer of antibody specific for gonadotropin-releasing hormone (GnRH) correlates with the regression of testes. Fusion proteins composed of canine GnRH and T helper (Th) cell epitope p35 originated from canine distemper virus (CDV) F protein and goat rotavirus VP6 protein were produced in E. coli. When these fusion proteins were injected to male dogs which were previously immunized with CDV vaccine, the fusion protein of GnRH-CDV Th cell epitope p35 induced much higher antibody than that of GnRH-rotavirus VP6 protein or GnRH alone. The degeneration of spermatogenesis was also verified in the male dogs immunized with the fusion protein of GnRH-CDV Th cell epitope p35. These results indicate that canine GnRH conjugated to CDV Th cell epitope p35 acted as a strong immunogen and the antibody to GnRH specifically neutralized GnRH in the testes. This study also implies a potential application of GnRH-based vaccines for immunocastration of male pets.

Advances in the study of epididymal protease inhibitor / 中华男科学杂志

The epididymal protease inhibitor (Eppin) has recently been cloned in human and mice, which is specifically expressed in the epididymis and testis. Eppin is a cystine-rich secretory protein which contains signal peptide, WAP and BPTI motifs. Eppin is involved in sperm maturation and fertilization, and in the innate immune system of human epididymis. Immunocontraception with Eppin is effective and reliable, but its safety is to be further proved. This paper summarizes the effects of Eppin of fertilization and immunity, as well as its utilization in immunocontraception.

Advances in the research of sperm protein 17 / 中华男科学杂志

Sperm protein 17 (Sp17) is a testis-specific protein involved in acrosome reaction in spermatozoa. However, the Sp17 gene has been recently detected in normal non-testis tissues and malignant neoplasias. Therefore Sp17 may be a potential target for immunocontraception and a suitable target for tumor immunotherapy. This paper reviews the advances in the protein characterization, expression and distribution, and biological function of Sp17 and its clinical research.

Progress in researches on sperm antigen fertilin beta / 中华男科学杂志

Fertilin beta plays an important role in fertilization by its disintegrin domain as a sperm-specific antigen. This paper reviews its structure, localization and roles in fertilization, and suggests that fertilin beta, as an important target antigen, has a very promising value in the development of human immunocontraceptive vaccine.

Zona pellucida glycoproteins based immunocontraceptive vaccines: strategies for development and their applications.

The mammalian oocyte is surrounded by an extra-cellular matrix, the zona pellucida (ZP), composed of three major glycoproteins (ZP1, ZP2 and ZP3). The ZP glycoproteins, by virtue of their tissue specificity and critical role during mammalian fertilization, have emerged as potential candidate antigens for the development of an immunocontraceptive vaccine. Molecular characterization of ZP glycoproteins from several species, reveals a variable degree of homology among the deduced primary amino acid sequences, which provided an opportunity to undertake active immunization studies in heterologous animal models. Active immunization of various animal species with either native ZP glycoproteins or those obtained by recombinant DNA technology led to the inhibition of fertility. Thus ZP glycoproteins based immunocontraceptive vaccines offer an attractive proposition for controlling wild life population. To make it a practical proposition, additional research inputs are required to optimize and devise novel strategies for vaccine delivery. Observed ovarian dysfunction, often associated with immunization by ZP glycoproteins is one of the major stumbling blocks for their use in humans. Ongoing studies to delineate appropriate B cell epitopes of ZP glycoproteins that are devoid of oophoritogenic T-cell epitopes, which will inhibit fertility without concomitant oophoritis, will be critical to determine their feasibility for human use.

Antígenos de zona pelúcida en el ovocio humano: su importancia en las estrategias anticonceptivas / Zona pellucida antigens of human oocyte: its relevance in contraceptive strategies

La zona pelúcida (ZP) es una capa de glicoproteínas que rodea al ovocito de los mamíferos. Esta cubierta está formada por tre familias de glicoproteínas denominadas ZP1, ZP2 y ZP3, que difieren en sus propiedades inmunológicas y funcionales debido a modificaciones postraduccionales. Estudios llevados a cabo en el ratón sugieren que la función de estas proteínas se encuentra relacionada con el reconocimiento del espermatozoide por la ZP, confiriéndole muy probablemente la connotación de receptores. Esta observación ha permitido que varios laboratorios hayan iniciado la producción y obtención de las proteínas de la ZP, permitiendo la exploración de su papel en procesos fisiológicos y clínicos, y ha abierto la posibilidad de utilizarlas en el desarrollo de un método inmunológico anticonceptivo. En la actualidad la posibilidad de obtener anticuerpos específicos contra los constituyentes proteínicos de la ZP representa una estrategia novedosa para el control de la fertilidad en el humano.

Research in reproduction: the Indian scenario in the last decade [II].

Developing new, improved and totally safe, effective and acceptable contraceptives based on the recent advances in cellular and molecular biology of reproduction is a new challenge to biomedical scientists involved in research in reproductive biology. The present article reviews some of the major contributions made during the last decade by scientists working in India in developing new strategies and technologies for better human reproductive health and fertility regulation.

Inmunización con hormona liberadora de gonodatropinas / Immunization with gonodatropins-releasing hormone

El uso de la inmunización contra la hormana liberadora de gonadotropinas (GnRH), es un método empleado con fines contraceptivos. Se estudió el efecto de una vacuna de GnHR unida al toxoide diftérico sobre el aparato reproductor de la rata blanca adulta y los niveles plasmáticos de testosterona (T). Se encontró que al tercer mes de haber sido inmunizados los animales con GnHR se produjo una significativa pérdida de peso de los testículos, vesículas seminales y próstata. El peso corporal no se afectó. Al estudio histológico se encontró que en los testículos existía una marcada afectación en la espermatogénesis, llegando en algunos animales a haber solamente células de Sertoli. Se concluye que la combinación empleada de GnHR con el toxoide diftérico, así como el esquema de vacunación empleado afectan profundamente al aparato reproductor de la rata. Desconocemos si el proceso deletéreo inducido por la vacunación es reversible o no

Seminal inhibin--prospects for immunocontraception.

Passive immunization of adult rats, hamsters and marmosets with rabbit anti-seminal inhibin resulted in complete or partial block of fertility. The antiserum treatment presumably neutralized endogenous inhibin resulting in an unopposed rise in circulating FSH. This probably led to a refractoriness of the testes to FSH resulting in complete spermatogenic arrest. Nevertheless, there was no change in the mating behaviour of the animals. The antibodies also affected the epididymal spermatozoa by causing large scale agglutination.

Antifertility effects in rats actively immunized with 80 kDa human semen glycoprotein.

A 80 kDa human sperm antigen has been identified using the serum of an infertile woman having circulating antisperm antibodies. The antigen was then purified to homogeneity by gel permeation chromatography using HPLC (protein PAK-125 column) system and on FPLC (superose-12 column) system. The antigen was found to be a glycoprotein. The antigen was mainly localized in the postacrosomal region of the human sperm, while it was localized in the head region of the rat sperm as demonstrated by immunofluorescent staining. The presence of this antigen was also demonstrated in the human prostate and endometrium and in the rat testis; epididymis and the prostate by immunocytochemical staining. The purified protein upon active immunization in female rats caused infertility in 100 percent animals. While in male rats it caused infertility in 90 percent animals. On morphometric analysis of testicular tissue it was observed that there was no significant change in spermatogonia and spermatocytes, but significant decrease in spermatids and sperm number as well as daily sperm production in the immunized male rats. The epididymal spermatozoa were markedly reduced in number and were largely found to be agglutinated. The results suggest that 80 kDa human sperm antigen appears to be a suitable candidate for immunocontraception both in male and female.

A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat.

Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses.