Search PubMed⌕ Search

Biomedical subjects

G R Dreesman

Publications and source records attributed to G R Dreesman.

At least 37 records · Page 2Linked to original sources

Induction of anti-HIV neutralizing antibodies by synthetic peptides.

Two synthetic peptides containing amino acid sequences analogous to the envelope glycoprotein of human T-lymphotropic virus (HTLV) type III (HTLV-III) and lymphadenopathy associated virus (LAV) were produced and used to immunize rabbits. The subsequent rabbit antisera neutralized HTLV-III infectivity in vitro. The two synthetic peptides corresponded to regions associated with the gp120 or gp41 subunits respectively, of human immunodeficiency virus (HIV). This data indicates that at least two neutralizing epitopes are present on the envelope glycoprotein of HIV and these epitopes are associated with two distinct virus envelope glycoproteins. Antisera generated against these peptides neutralized infectivity of two different isolates of HTLV-III. The data is discussed in terms of possible strategy for developing an effective vaccine against the etiologic agents of acquired immune deficiency syndrome (AIDS).

Amino Acid Sequence↗

Response to a hepatitis B polypeptide vaccine in micelle form in a young adult population.

Polypeptide micelles with relative molecular weights of 25,000 (p25) and 30,000 (gp30) daltons were prepared from native 22-nm hepatitis B surface antigen (HBsAg) particles. This p25/gp30 complex was alum-adsorbed, and three dosage levels (20 micrograms, 4 micrograms, and 0.8 micrograms) were administered at 0, 1, and 6 months to 51 human volunteers. Local and systemic reactions were clinically insignificant, and all vaccinees seroconverted, regardless of dose. As anticipated, antibody responses diminished as the dosage was reduced. Seroconversion rates and geometric mean antibody levels for the 20 micrograms dosage group were significantly better than those observed with a commercial vaccine and were comparable to those achieved after immunization with 40 micrograms of the intact 22-nm particles used to prepare the polypeptides. By 2 weeks, an anti-HBs response was elicited in 80% of the group receiving 20 micrograms of the polypeptide vaccine. This rapid response to immunization may be particularly beneficial for postexposure prophylaxis where the early development of immunity is advantageous.

Adult↗

Further characterization of internal image-bearing anti-idiotypic antibodies: specific binding to immunoglobulin receptors on murine hybridoma cells secreting antibodies to hepatitis B surface antigen.

The further characterization of internal image anti-idiotypic antibodies (anti-Id) that represent a potential alternative vaccine candidate for type B viral hepatitis is described. The anti-Id preparation contains an internal image component or related epitope that mimics hepatitis B surface antigen (HBsAg) and binds to murine hybridoma cells that secrete antibodies to HBsAg (anti-HBs). This binding to anti-HBs-secreting hybridomas was partially inhibited by intact HBsAg particles and was associated with the expression of an interspecies idiotype. Immunoprecipitation studies demonstrated that the anti-Id bound to immunoglobulin molecules expressed on the surface of the hybridoma cells. These data suggest that internal image anti-Id, which induces an in vivo antibody response by antigenic mimicry in the absence of HBsAg, binds to anti-HBs molecules on the surface of cells actively secreting anti-HBs. The possible mechanism for internal image anti-Id-based antibody vaccines that mimic the overall conformation of antigens associated with infectious agents is discussed.

Animals↗

Suppression of in vivo tumor formation induced by simian virus 40-transformed cells in mice receiving antiidiotypic antibodies.

This study characterizes four private idiotypes (Id) associated with monoclonal antibodies (mAb) to simian virus 40 (SV40) tumor antigen (T-Ag), and to a cellular protein, p53. Anti-Id recognized Id determinants associated with the antibody-combining site. BALB/c mice receiving a pool of anti-Id directed against mAb recognizing distinct amino and carboxyl terminal epitopes of T-Ag before receiving a tumorigenic dose of SV40-transformed cells showed suppression of tumor formation. Serum obtained from these mice before tumor challenge contained anti-anti-Id that failed to bind T-Ag. These data support the potential role of regulatory idiotopes in tumor immunity.

Animals↗

A prospective study of herpes simplex virus infection in a defined population in Houston, Texas.

A seroepidemiologic study was conducted to determine the incidence of antibodies to herpes simplex virus in a population of middle-class Caucasian women. In utero exposure to diethylstilbestrol did not influence the frequency of herpes simplex virus infection. The frequency of infection increased with age and number of sex partners and a 50% increase in incidence of herpes simplex virus type 2 infection was noted during the 4-year period of the study. Subclinical herpes simplex virus type 2 infections apparently occurred in some women without preexisting antibodies to herpes simplex virus type 1.

Adult↗

A prospective study of association of herpes simplex virus and human papillomavirus infection with cervical neoplasia in women exposed to diethylstilbestrol in utero.

One thousand one hundred thirty-four women, enrolled in a prospective study of the development of cervical neoplasia in women exposed to diethylstilbestrol (DES) in utero, were examined at least once a year. Twenty-three women developed cervical intraepithelial neoplasia (CIN) of different degrees during the 7-year follow-up period and were matched with women who did not develop CIN during the study period. Serum samples were obtained at the time of entry into the study and at the time of diagnosis of neoplasia. In the control group, a second serum sample was obtained close to the time when CIN was diagnosed in the other group of women. The sera were studied for antibodies to both types of herpes simplex virus (HSV) by microneutralization assay and by a radioimmunoassay using, as antigens, glycoproteins VP123 for HSV type 1 and VP119 for HSV type 2. Women who developed CIN had, in the enrollment specimen which preceded the neoplasia, a higher rate of antibodies to HSV-1 than did the matched controls (22%), while the two groups did not differ in frequency of antibodies to HSV-2 (9%). Similar differences were observed in the sample drawn at the time of diagnosis of CIN. Women who later developed CIN and had, at the time of entry into the study, cervical epithelial changes associated with DES exposure, were infected with HSV-1 at a higher rate than women who remained free of neoplasia or women with CIN but without DES-associated cervical epithelial changes. Morphologic evidence of associated papillomavirus (HPV) infection was observed in 74% of CIN cases and no such observation was made in biopsy specimens taken prior to development of CIN. Morphologic evidence of HPV infection was found in a women of the control group having squamous metaplasia. HPV structural antigens were found in 3 of 10 CIN I and CIN II cases, and none in the CIN III specimens. The possible role of the HSV and HPV infection in the pathogenesis of cervical neoplasia is discussed.

Adolescent↗

Synthetic hepatitis B surface antigen peptide vaccine.

A synthetic hepatitis B surface antigen (HBsAg) peptide was prepared containing amino acid residues 122-137 of the major HBsAg polypeptide. This peptide was cyclized by the introduction of an intrachain disulfide bond between cysteine residues at positions 124 and 137 because previous studies had shown that intact disulfide bonds are critical for maintenance of HBsAg activity. An anti-HBs response was produced in mice by free peptide entrapped in liposomes. However, the immunogenicity was enhanced by aggregation into micelles, and by coupling to tetanus toxoid. Analysis of the peptide with a panel of monoclonal antibodies showed that peptide 122-137 contained a conformation (discontinuous) group a epitope and a sequential (continuous) subgroup y epitope. In addition, the cyclic peptide inhibited a human anti-HBs idiotype-anti-idiotype reaction with specificity for group a determinant(s). The potential for synthetic peptides for hepatitis B virus vaccine development is discussed.

Animals↗

Antigen mimicry by anti-idiotype antibodies that recognize a common anti-hepatitis B surface antigen idiotype.

Anti-idiotype antibodies that recognize a common human idiotype present on antibodies to hepatitis B surface antigen (anti-HBs) from individuals naturally infected by hepatitis B virus (HBV) and an interspecies idiotype on anti-HBs produced by active immunization with hepatitis B surface antigen (HBsAg) were used in vivo to modulate idiotype networks in mice. Injection of anti-idiotype antibodies without subsequent HBsAg stimulation induced an anti-HBs response. The anti-idiotype-induced anti-HBs recognized the group-specific a determinant (s) of HBsAg, which has been shown to be responsible for induction of protective immunity to HBV in both chimpanzees and humans. In addition, the anti-HBs expressed an interspecies idiotype which is shared by humans naturally infected with HBV. Prior inoculation of mice with alum-adsorbed anti-idiotype potentiated the immune response to a subsequent inoculation with either native HBsAg particles or with a synthetic HBsAg peptide. These data suggest the potential use of anti-idiotype antibodies as a vaccine or vaccine potentiator for HBV.

Animals↗

Application of a modified computer algorithm in determining potential antigenic determinants associated with the AIDS virus glycoprotein.

A computer program was developed for use on an Apple IIe that utilized the parameters developed by Hopp and Woods (T. P. Hopp and K. R. Woods, 1983, Mol. Immunol. 20, 483-489) for predicting the hydrophilic regions of a given protein. This program will produce a listing of the hydrophilic sequence averages and graphically illustrates the peak areas. The hydrophilic averages over a hexapeptide length can be used to predict protein structure. In conjunction with the Chou-Fasman predictive scheme for protein secondary structure determination, the possible antigenic determinants for the envelope glycoprotein of three viruses isolated from patients with acquired immunodeficiency syndrome (AIDS) were predicted. These predicted determinants could be used to generate synthetic peptides that represent a potential vaccine preparation or in developing a diagnostic assay that specifically detects the agent.

Acquired Immunodeficiency Syndrome↗

In vivo detection of human hepatoma secreting hepatitis B surface antigen in nude mice with radiolabeled monoclonal antibodies that recognize distinct epitopes.

Hepatitis B surface antigen (HBsAg), produced by a human hepatoma which had been transplanted into athymic nude mice, was specifically detected in vivo by 131I-labeled monoclonal antibodies (McAb) directed against distinct epitopes of HBsAg (anti-HBs). Significantly higher levels of radioactivity were present in the hepatoma secreting HBsAg when compared to either a non-HBsAg producing epidermoid tumor or most other tissues obtained from nude mice treated with the 131I-labeled anti-Hbs McAb. A radiolabeled control McAb that did not recognize HBsAg failed to discriminate between either the HBsAg positive and negative tumors or other tissues from nude mice. These data demonstrate the in vivo immunological specificity of anti-HBs McAb for HBsAg associated with a hepatoma tumor.

Animals↗

Biotin-avidin amplified ELISA for quantitation of human IgA.

A biotin-avidin amplified enzyme-linked immunosorbent assay (ELISA) for the measurement of human IgA in serum, colostrum, gastric juice, and supernatants of in vitro mitogen-stimulated human peripheral blood mononuclear cells is described. The ELISA reproducibly detects as little as one nanogram of IgA in a fifty microliter sample (20 ng/ml).

Avidin↗

Detection of human acid alpha-glucosidase in fibroblasts using monoclonal antibodies in a biotin-avidin amplified ELISA.

A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase was developed using a mouse monoclonal antibody incorporated into a biotin-avidin amplified ELISA. The immunoassay was more than 60 times more sensitive than the currently used enzymatic assay for alpha-glucosidase activity using a fluorimetric substrate. This methodology provides an alternative approach with increased sensitivity for screening individuals for alpha-glucosidase deficiency.

Antibodies, Monoclonal↗

Longitudinal study of HTLV-III-infected chimpanzees by lymphocyte subpopulation analysis.

Following inoculation with plasma from human patients with AIDS, two chimpanzees demonstrated specific antihuman T-cell leukemia virus type 3 (HTLV-III) antibodies. One of the two chimpanzees also developed massive lymphadenopathy that persisted for 32 weeks and demonstrated a concurrent and more frequent depression of total T cells (T3) and T helper cells (T4) with a decrease in the ratios of T4 to T suppressor cells (T8). These results indicate that chimpanzees demonstrate a range of T-cell subpopulations during infection and disease induced by HTLV-III.

Acquired Immunodeficiency Syndrome↗

Enhancement of viral hepatitis B antibody (Anti-HBs) response to a synthetic cyclic peptide by priming with anti-idiotype antibodies.

In vivo injections of anti-idiotype antibodies were used to prime the immune system of mice to hepatitis B surface antigen (HBsAg). Anti-idiotype reagents in conjunction with a cyclic synthetic peptide analogous to positions 122-137 of HBsAg induced an antibody response to HBsAg (anti-HBs) comparable to that obtained with a single injection of intact HBsAg particles. In addition, high anti-HBs titers were produced in mice injected with HBsAg following anti-idiotype priming. These data indicate that anti-idiotype antibodies may be useful in priming the immune system of a host to a potential infectious agent.

Animals↗