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At least 217 records · Page 12Linked to original sources
PubMed1993

Comparison of conventional adjuvants and 'adjuvant-free' monoclonal antibody targeting for stimulating antibody responses against a conjugate of luteinizing hormone releasing hormone and avidin.

A conjugate of luteinizing hormone releasing hormone (LHRH) and avidin was used for immunizing mice and sheep. In mice, a range of adjuvants co-administered with the conjugate was shown to affect antibody titre and isotype. The commercially available Montanide and Ribi adjuvant emulsions, polyadenylic-polyuridylic acid, Quil A and Freund's complete adjuvant all produced high antibody titres to LHRH (reciprocal titre range 8000-20,000) and avidin (range 9000-35,000). Alhydrogel, Pluronic gel, Immunostim, DEAE-Dextran and muramyl dipeptide were weak to moderately effective (reciprocal titre ranges of 1300-5000 for LHRH and 3000-6000 for avidin, respectively). With Quil A, the response to avidin in mice was found to consist of roughly equal proportions of the IgG1, IgG2a and IgG2b isotypes. In contrast, the response to avidin using the other adjuvants and to LHRH consisted predominantly of the IgG1 isotype. An 'adjuvant-free' immunization strategy was attempted by targeting the LHRH-avidin conjugate to class II major histocompatibility complex (MHC) determinants on cells of the immune system. Using an immunoconjugate formed by linking LHRH-avidin to an antibody specific for mouse and sheep class II molecules, a twofold augmentation of titres relative to controls was obtained in mice. These antibodies were almost exclusively of the IgG1 isotype. In contrast, monoclonal antibody targeting in sheep resulted in a significantly enhanced immune response (reciprocal titres of 15,000 and 20,000 for LHRH and avidin, respectively) which was comparable to that achieved by immunizing with Quil A as adjuvant. Both the monoclonal antibody targeting and Quil A treatments tended to favour the production of antibody isotype IgG1 over IgG2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1997

A bait-delivered immunocontraceptive vaccine for the European red fox (Vulpes vulpes) by the year 2002?

An orally-delivered immunocontraceptive vaccine is being developed for the control of fox populations. A number of genes (PH-20, LDH-C4, ZP3) encoding gamete proteins have been cloned, produced in recombinant expression systems and used in fertility trials to test the efficacy of these antigens. As the immunocontraceptive vaccine will be delivered in a bait, there is a requirement for a greater understanding of the immune responses of the reproductive mucosa in canids, and the assessment of the best vaccine delivery system that will evoke a mucosal antibody response. Several vaccine delivery systems including microencapsulated antigens, and both vaccinia virus and bacterial vectors are being investigated. Oral administration of Salmonella typhimurium recombinants expressing different fox sperm antigens stimulates both systemic IgG responses to the antigen and a mucosal immune response within the female reproductive tract in the fox, indicating that salmonella may have potential with respect to the oral delivery of antigen. The enhancement of mucosal immune responses to orally-delivered vaccines is also being examined, research focussing on the possible use of fox-specific cytokines or the beta-subunit of cholera toxin in forming part of the vaccine construct.

Adjuvants, Immunologic↗
PubMed1991

A survey of biotechnology.

This issue on immunology and biotechnology opens with a survey of the contribution of immunology to medicine. Proteins, growth and differentiation factors, and monoclonal antibodies to surface antigens will have an impact in the 1990's likely similar to that of antibiotics in the 1950's. The characterization of factors and cell-surface molecules opens the investigation of the role of "recessive oncogenes" in the development of cancer. A further impact of immunology in the classical field of prophilaxis is represented by the innovative development of contraceptive vaccines based on the use of episomal shuttle vectors for the expression of surface sperm proteins able to induce an effective immune response.

Antibodies, Monoclonal↗
PubMed1991

Preliminary studies on the indium slide immunoassay for estimation of human chorionic gonadotropin and antihuman chorionic gonadotropin antibody.

Human chorionic gonadotropin (hCG) is synthesized and secreted as early as 170 hr after fertilization and has been used as an index for pregnancy. Neutralization of hCG with a beta-subunit hCG vaccine(s) has been proposed as a contraceptive technique. To monitor the duration of effectiveness of the vaccine, it will be necessary to monitor the anti-hCG antibodies, especially those responsible for inhibiting the hCG bioactivity. We report a simple, rapid technique using an indium slide immunoassay for the qualitative estimation of hCG and to monitor a bioeffective anti-hCG antibody. The sensitivity of the indium slide assay to measure hCG ranged from 1 microgram/ml to 1 ng/ml, depending on the format of the assay. The indium slide assay also detected anti-hCG antibodies generated against a specific determinant on hCG recognized by a neutralizing monoclonal antibody (P3W80) in women immunized with a contraceptive vaccine.

Antibodies↗
PubMed1993

Antibody response against epitopes on hCG mapped by monoclonal antibodies in women immunized with an anti-hCG vaccine and its implications for bioneutralization.

The immunological determinants on hCG, to which an antibody response is generated in women by the contraceptive HSD vaccine, were mapped by using a panel of anti-hCG monoclonal antibodies. Two types of inhibition enzyme immunoassays (EIAs) were used to analyze 126 serum samples from 18 subjects immunized with the vaccine and protected from pregnancy. Monoclonal antibody (MAb) 357-2, which recognizes beta-hCG loop peptide 38-57, did not inhibit significantly the binding of immune sera to hCG. Moreover, none of the sera reacted with this loop peptide in a direct binding EIA, suggesting weak immunogenicity of this epitope. All sera competed with MAb 206 and a preponderance of antibodies was seen against this epitopic region on beta-hCG. The antibody titers against the MAb 206 epitope showed a good correlation with the bioneutralization capacity of the sera throughout the course of immunization. These studies indicate the presence of an immunodominant antigenic determinant on hCG as recognized by the human immune system.

Animals↗
PubMed1989

Antibody response and characteristics of antibodies in women immunized with three contraceptive vaccines inducing antibodies against human chorionic gonadotropin.

Data are presented on antibody titers generated in 88 women immunized with three formulations of antihuman chorionic gonadotropin (hCG) vaccine, namely, beta-hCG (formulation B); beta-hCG associated with alpha-subunit of ovine luteinizing hormone (LH) (formulation A) and beta-hCG + beta-ovine LH (formulation M), each linked to tetanus toxoid and cholera toxin chain B as carriers. Each formulation was tested at two dose levels (100 and 500 micrograms). All women without exception developed anti-hCG antibodies having hCG-binding capacity above 20 ng mL-1 (0.5 nM), a level considered to be the threshold for prevention of pregnancy. Formulations A and B gave relatively better immunogenic response in human subjects than M. In each case, the antibody response was reversible. The mean duration of response above 20 ng was 35 to 37 weeks for formulation A, 34 weeks for B, and 17 to 20 weeks for M. Antibodies induced by three formulations of the vaccine had high-affinity (Ka 10(9)-10(10)M-1) for binding with hCG. They were devoid of cross-reaction with human follicle-stimulating hormone and thyroid-stimulating hormone but, as expected, cross-reacted with human LH. Antibodies were competent to block the hCG induced ovarian hyperemia.

Adult↗
PubMed1986

Use of synthetic peptides as immunogens for developing a vaccine against human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by the placental trophoblast soon after conception and is essential for successful gestation in women. A vaccine against this hormone has been developed for the purposes of birth control and the treatment of hormone-related diseases. Synthetic peptides representing the native primary structure of the hCG beta subunit have been coupled to protein carriers to produce immunogens. Several peptides, representing varying lengths from the C-terminus of the beta subunit, were synthesized and their ability to elicit antibodies reactive to hCG and able to neutralize hCG activity in vivo was tested. A peptide representing the 37 amino acids of the C-terminal end of the beta subunit was selected as the vaccine antigen and diphtheria toxoid was selected as the carrier for the first prototype vaccine. Procedures for coupling a specified number of peptide molecules to each carrier molecule in a reproducible fashion were developed. The immunogen is mixed with an adjuvant compound and the mixture administered in an oil-in-water emulsion. Significant levels of antibodies to hCG have been elicited in several species and a marked reduction in the fertility of immunized baboons has been observed. Extensive evaluations of vaccine safety have been conducted and Phase I clinical trials have been proposed to test its utility for human birth control. Possible applications of the hCG vaccine to health problems other than birth control are being considered.

Adjuvants, Immunologic↗
PubMed1985

Formulation of a potential antipregnancy vaccine based on the beta-subunit of human chorionic gonadotropin (beta-hCG). I. Alternative macromolecular carriers.

The antibody response obtained after vaccinating rabbits with the beta-subunit of human chorionic gonadotropin (beta-hCG) linked to several protein and polysaccharide carriers was measured. In all but one preparation, carbodiimide was used to couple the beta-hCG to the carrier. Tetanus toxoid (TT) and cholera vaccine proved the most effective carriers among those examined. TT from different manufacturers proved to be greatly different in free amino group content and differed in ability to participate in the coupling reaction. Reasonably good replication of the coupling reaction was obtained with different production lots from the same manufacturer. Inferior antigenic response was obtained with the products of coupling beta-hCG to H. pertussis, influenza vaccine, polylysine, pneumococcus polysaccharide, or E. coli polysaccharide. The findings indicate TT and cholera vaccine to be especially effective in enhancing the antigenicity of a weakly antigenic peptide but point to significant differences in the TT from different manufacturers.

Adjuvants, Immunologic↗
PubMed1994

Human testis cDNAs identified by sera from infertile patients: a molecular biological approach to immunocontraceptive development.

Sera from patients with known or suspected immunological infertility were used to screen a human testis cDNA library. A total of 59 sera detected 38 unique cDNA inserts of which four were testis specific by Northern blot analyses. One of these is a testis-specific isoform of calpastatin. Five additional clones, although not testis specific, were found to be testis abundant. The number and type of clones identified by these human sera suggests a possible aetiology for immunologic infertility. The testis-specific clones will be further characterized to establish their usefulness as contraceptive vaccine candidates.

Antigens↗
PubMed2002

Molecular and immunological characteristics of sperm antigens involved in egg binding.

Development of a vaccine(s) based on sperm antigens represents a promising approach to contraception. The utility of an antigen in immunocontraception is contingent upon sperm/testis-specificity and its involvement in the fertilization process. Since, the sperm-zona pellucida (ZP) recognition and binding constitutes the most important event in the fertilization process, molecules involved at this site are attractive candidates for immunocontraception. Using hybridoma technology, subtractive hybridization, and differential display technology, our laboratory has delineated several sperm antigens. These antigens have testis-specific expression and have a role in the fertilization process. The cDNAs encoding for the antigens have been cloned and sequenced. Among these, the fertilization antigen (FA-1) is particularly interesting, because it is involved in immuno-infertility in humans. Using the phage peptide display technique, a novel dodecamer sequence of a approximately 72+/-5 kD antigen, designated as YLP(12), that is testis-specific and involved in human sperm-ZP recognition/binding, was identified. A synthetic 12-mer peptide was generated based on this sequence. In the hemizona assay, YLP(12) peptide and its monovalent Fab' antibodies specifically and significantly inhibited human sperm-ZP binding. Furthermore, the presence of specific antibodies reactive with YLP(12) peptide, were identified in the serum and seminal plasma of immuno-infertile men. Thus, FA-1 and YLP(12) are promising target antigens for the development of contraceptive vaccines as well as for specific diagnosis and treatment of male infertility.

Antigens, Surface↗
PubMed1993

Inhibition of fertility in female mice by immunization with a B-cell epitope, the synthetic sperm peptide, P10G.

Human patient sera containing antisperm antibodies (from vasectomized men and infertile women) immunologically react with the synthetic peptide P10G (PGGGTLPPSG), and affinity purified antibodies to P10G (anti-P10G) react with human spermatozoa (O'Rand et al., 1990). In this study P10G was used to elicit antibodies and the effect of the antibodies on fertility in female mice determined. The P10G sequence is derived from the 14-kDa rabbit sperm autoantigen, RSA (O'Rand and Widgren, 1990). The results of this study demonstrate that female mice can become infertile when immunized with the synthetic peptide P10G conjugated to the carrier protein keyhole limpet hemocyanin (KLH). However, the results also show that it is important to distinguish those mice with high serum antibody levels from those with lower levels. Infertility was clearly apparent in the high titer subgroup with an 80% decrease in pregnancy rate during the last of three matings and a 71% decrease in litter size over all three matings when compared to the low titer subgroup or the control groups. Significantly, mice immunized with P10G without carrier protein show no detectable antigen specific proliferation of lymph node cells in response to 100 microM of the peptide. P10G is not a T-cell epitope, but rather a B-cell epitope and it does not elicit an autoimmune response in the female mouse. This demonstration in mice is an important first step in the development of a safe human immunocontraceptive vaccine.

Adjuvants, Immunologic↗