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Biomedical subjects

D H Zimmerman

Publications and source records attributed to D H Zimmerman.

At least 19 recordsLinked to original sources
PubMed2001

Induction of cross clade reactive specific antibodies in mice by conjugates of HGP-30 (peptide analog of HIV-1(SF2) p17) and peptide segments of human beta-2-microglobulin or MHC II beta chain.

HGP-30, a 30 amino acid synthetic peptide homologous to a conserved region of HIV-1(SF2) p17 (aa86-115), has previously been shown to elicit both cellular and humoral immune responses when conjugated to KLH and adsorbed to alum. However, the free HGP-30 peptide is not immunogenic in animals. In order to improve the immunogenicity of HGP-30, peptide conjugates consisting of a modified HGP-30 sequence (m-HGP-30/aa82-111) and a peptide segment, residues 38-50, of the MHC I accessory molecule, human beta-2-microglobulin (beta-2-M), referred to as Peptide J, or a peptide from the MHC II beta chain (peptide G) were evaluated in mice. The effects of carriers and adjuvants on serum antibody titers, specificities to various HIV-1 clade peptides similar to HGP-30 and isotype patterns were examined. Peptides J or especially G conjugated to modified-HGP-30 (LEAPS 102 and LEAPS 101, respectively) generated comparable or better immune responses to modified HGP-30 than KLH conjugates as judged by the induction of: (1) similar antibody titers; (2) broader HIV clade antigen binding; and (3) antibody isotype response patterns indicative of a TH1 pathway (i.e. increased amounts of IgG2a and IgG2b antibodies). The ISA 51 and MPL(R)-SE adjuvants induced higher antibody responses than alum, with the ISA 51 being more potent. Immune responses to LEAPS 102, as compared to LEAPS 101, were weaker and slower to develop as determined by antibody titers and cross clade reactivity of the antibodies induced. Compared to KLH conjugates which induced significant anti-KLH antibody titers, minimal antibody responses were observed to peptide G, the more immunogenic conjugate, and peptide J. These results suggest that modified HGP-30 L.E.A.P.S. constructs may be useful as HIV vaccine candidates for preferential induction of TH1 directed cell mediated immune responses.

AIDS Vaccines↗
PubMed2000

Flt3 ligand enhances the immunogenicity of a gag-based HIV-1 vaccine.

Liposomes and Flt3 ligand (Flt3L), a ligand for the fms-like tyrosine kinase receptor Flt3/ FLK2, can augment the immune response to an HIV peptide vaccine. The HGP-30 peptide used in these studies is a synthetic peptide that corresponds to a highly conserved region of HIV-1 p17 gag (amino acids 86-115). Mice were immunized with HGP-30 or HGP-30 conjugated to keyhole limpet hemocyanin (KLH) and delayed-type hypersensitivity (DTH) responses, antibody (IgG) amount and antigen-specific proliferative responses by spleen cells were used to monitor the immune response. Daily injections of Flt3L prior to HGP-30 administration enhanced significantly an antigen-specific lymphocyte proliferation response when compared with Flt3L, HGP-30 alone or HGP-30 containing liposomes. Intravenous administration of HGP-30 was superior to intramuscular (i.m.) immunization for the induction of DTH responses. The HGP-30/KLH containing liposomes enhanced both DTH and antibody responses, while liposomes containing HGP-30 peptide elicited only T cell responses. In these studies, either Flt3L or liposomes increased DTH responses compared with the i.m. injection of the HGP-30 vaccine alone.

AIDS Vaccines↗
PubMed1998

Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid synthetic peptide antigen from HIV type 1 p17.

HGP-30, a 30-amino acid synthetic peptide analog of HIV-1SF2 p17 (aa 86-115), was used to immunize both mice and humans. Since the amino acid sequence of HGP-30 is relatively conserved among different HIV-1 strains and clades, experiments were carried out to determine if antisera obtained by immunizing animals and humans can recognize HGP-30-related peptide consensus sequences belonging to different clades. Results show that antisera from mice immunized with HGP-30 can recognize clade B and C and to a lesser degree clade A and E consensus sequences of HIV-1, in addition to recognizing HGP-30 sequence. The cross-clade recognition was higher in mouse sera obtained on day 42 than on day 14 or 28. MPL/SE and Novasomes were better adjuvants than alum in inducing antibodies that showed cross-clade recognition and IgG2a and IgG2b antibody isotypes. Similar cross-clade recognition was observed in several sera from humans immunized with an HGP-30/KLH/alum formulation. The human sera from HGP-30-immunized subjects evaluated for cross-clade recognition of HGP-30 peptides were from subjects whose cells showed significant protection from HIV infection on virus challenge in the hu-PBL-SCID mouse model. These studies suggest that HGP-30 may be useful as a candidate vaccine antigen for populations in countries with prevalence of different HIV clades.

AIDS Vaccines↗
PubMed1986

AIDS retrovirus antibodies in hemophiliacs treated with factor VIII or factor IX concentrates, cryoprecipitate, or fresh frozen plasma: prevalence, seroconversion rate, and clinical correlations.

Antibodies to the AIDS retrovirus, specifically to human T cell lymphotropic virus, type III, and AIDS-associated retrovirus, were detected with increasing prevalence in a population of 190 hemophiliacs from western Pennsylvania between 1981 and 1984: 7.7% in 1981, 20.0% in 1982, 45.5% in 1983, and 62.5% in 1984. The seropositive included approximately three fourths of those receiving factor VIII concentrate, nearly one third of those receiving factor IX concentrate, nearly one fifth of those receiving cryoprecipitate, and none of those receiving fresh frozen plasma. The seroconversion rate, determined on 43 seropositive hemophiliacs from this group who were serially sampled, was 0% in 1977, 4.7% in 1978, 4.9% in 1979, 2.6% in 1980, 10.5% in 1981, 52.9% in 1982, 87.5% in 1983, and 100% in 1984. Of 27 seropositive for three or more years (since 1982 or before), four (15%) have developed AIDS and seven (26%), diffuse lymphadenopathy (ARC); of 16 seropositive for less than three years, none has developed AIDS and three (19%) have developed ARC. The mean time from seroconversion to onset of ARC, 0.8 +/- 0.2 years (SEM), was shorter (P less than .001) than the time to onset of AIDS, 4.1 +/- 0.6 years. These findings confirm the widespread presence of AIDS retrovirus and support the association of these retroviruses with the acquired immunodeficiency syndrome and related conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Identification and typing of herpes simplex virus types 1 and 2 by monoclonal antibodies, sensitivity to the drug (E)-5-(2-bromovinyl)-2'-deoxyuridine, and restriction endonuclease analysis of viral DNA.

With development of antiviral drugs, the need to identify a virus as to drug sensitivity becomes increasingly of importance. The compound (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) has been shown to be much more inhibitory to the replication of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus as opposed to herpes simplex virus type 2 (HSV-2). We have typed over 170 isolates, using an immunofluorescent technique and sensitivity to the drug BVDU. These results were then compared to the typing of isolates by analysis of viral DNA after restriction endonuclease digestion (EcoRI). Without exception the results were in agreement between the monoclonal antibody results and sensitivity to the drug BVDU. Furthermore, the typing with monoclonal antibodies was also in excellent agreement with the DNA analysis. Only those isolates inhibited with BVDU showed DNA characteristics of HSV-1 and reacted only with the S-200 antibody. On the other hand, those isolates which reacted with the monoclonal antibody S-141 were insensitive to BVDU, and again this was in agreement with the DNA analysis. These results could provide the basis for developing a diagnostic test using the two monoclonal antibodies to type either isolates or direct smears and to use the results as a basis for possible drug therapy.

Antibodies, Monoclonal↗
PubMed1985

Lack of oral HSV-2 in a college student population.

A population of individuals with a high incidence of genital herpes simplex virus type 1 (HSV-1), due most likely to oro-genital contact, was examined to determine the incidence of oral herpes simplex virus type 2 (HSV-2) infection. Herpes simplex virus was isolated from the oral cavity of 43 college students whose symptoms ranged from singular lesions of the lips with minimal discomfort to severe oral disease with systemic involvement resulting in lymphadenopathy, chills, sweat, myalgia, and fever. The virus isolated from each case was identified by serum neutralization and typed as HSV-1 or HSV-2 using (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA. In every instance the isolate was HSV-1. Additional identification and typing of head and neck isolates as well as oral samples from non-university patients demonstrated that all were also HSV-1. Therefore, while HSV-1 appears to be readily transmitted to the genitalia in this group of individuals, the transmission of HSV-2 to the oral cavity may not be as common, even though clinical histories revealed that several of these patients were engaging in oro-genital contact.

Adult↗
PubMed1984

Incidence of herpes simplex virus types 1 and 2 in penile lesions of college men.

Herpes simplex virus (HSV) was isolated from penile lesions of 15 college men. Using (E)-5-(2-bromovinyl)-2'-deoxyuridine sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA, 4 of 15 (26%) isolates were found to be HSV-1, and 11 of 15 (74%) isolates were found to be HSV-2. It is likely that some of the genital HSV-1 infections are related to oral genital contact, but this fact could not be established for all cases, since the females in this group had previously been shown to have a high incidence of genital HSV-1.

Adult↗
PubMed1982

Rapid quantitation of serum immunoglobulins with a miniature centrifugal analyzer.

For these quantitative turbidimetric assays for immunoglobulins IgG, IgA, and IgM in serum, the reagents used are commercially available in kit form. The two-point assays are performed with a miniature centrifugal analyzer (GEMENI, Electro-Nucleonics, Inc.). The reading taken 5 s after mixing is used to correct for specimen turbidity. Run-to-run precision (CV) was typically 5% (range: 3.0-8.7%). Excellent correlation with radial immunodiffusion was observed for each test (r greater than 0.98 for each test). The dynamic range of each test extends above and below the reference-interval ranges.

Centrifugation↗
PubMed1980

The lipid A moiety of lipopolysaccharide is specifically bound to B cell subpopulations of responder and nonresponder animals.

Employing autoradiography to detect [125I]-lipid A binding splenocytes and immunofluorescence to identify splenic B cells, it was observed that only a subpopulation of B cells bound lipid A. In contrast, non-B cells, including T cells and macrophage cells, exhibited either relatively little or no lipid A binding. LPS-responder and LPS-nonresponder substrains of mice exhibited essentially the same distribution of bound [125I]-lipid A among B cell subpopulations. Approximately 25% of the B splenocytes obtained from the LPS-responsive C3H/HeN substrain or from the LPS-nonresponsive C3H/HeJ, C57BL/10ScCR and C57BL/10ScN substrains bound [125I]-lipid A. On the other hand, 60% of the B splenocytes from both high- and low-responder mice derived from the CBA strain exhibited [125I]-lipid A binding. Taken in conjunction with the findings of other workers, these results are consistent with the possibility that the genetic defect in nonresponder mice is related to a lipid A triggering event rather than to lipid A binding.

Animals↗
PubMed1977

Differentiation of lymphoid cells: the preferential binding of the lipid A moiety of lipopolysaccharide to B lymphocyte populations.

Lipid A, prepared from lipopolysaccharide, was labeled with 125 I. Such iodinated lipid A possesses the full mitogenic activity of untreated lipid A. Comparison of the 125 I-lipid A-binding activity of splenocytes and thymocytes from the same rabbit revealed that the extent of labeling of splenocytes was 10 to 20 times greater than that observed with an equivalent number of thymocytes. A similar preferential binding was detected in comparing cells in mouse and rat. Spleen populations depleted of adherent cells were essentially unaltered with regard to binding when compared to the original population. In addition, spleen cell populations enriched for thymus-derived cells (T cells) exhibited a marked loss of specific binding activity. On the other hand, spleen cell populations enriched for bone marrow-derived cells (B cells) exhibited the expected binding. The difference in binding behavior of B and T cell-enriched populations was confirmed by using three independent techniques to separate B and T cells. These findings are consistent with the mitogenic specificity of lipid A toward B cells rather than T cells and suggest that the observed cellular specificity resides in an early event in mitogenesis, i.e., binding of the mitogen.

Animals↗
PubMed1977

Solid-phase enzyme immunoassay for hepatitis B surface antigen.

A solid-phase enzyme immunoassay is described for measuring hepatitis B surface antigen in human serum or plasma. Immunologically purified antibody labeled with horseradish peroxidase was used as the indicator. In the assay system, antibody-coated controlled-pore glass is used as a solid support and there are three sequential incubations, totaling 2 h, at room temperature. Results for serially diluted positive and reference sera compare favorably to radioimmunoassay in sensitivity and specificity.

False Positive Reactions↗
PubMed1976

Differentiation of lymphoid cells. A selective anti-mitogenic component of normal serum which inhibits the induction of immunoglobulin production.

Rabbit lymph node cell populations cultured in vitro in the presence of fetal calf serum are induced to produce immunoglobulin M-secreting cells. The induction of such immunoglobulin production, measured by the capacity of the cell population to secrete immunoglobulins, was inhibited when cells were cultured with sera from a variety of species despite the presence of fetal calf serum. The addition of such inhibitory serum 36 hours after initiation of the cell culture or thereafter was without effect on the extent of induction of immunoglobulin production. On the other hand, the presence of inhibitory serum in culture during only the first 24 hours yielded the same inhibition as when serum was present throughout the 72-hour culture period. Inhibitory sera also suppressed the incorporation of thymidine into DNA. The induction of immunoglobulin production and the incorporation of thymidine into DNA were essentially equally inhibited by the same range of serum concentrations. Unlike conventional inhibitors of DNA synthesis, the inhibitory sera exhibited selective specificity with regard to the kind of cells that could be affected. Thus, such sera inhibited the DNA synthesis of lymph node cells cultured in the presence of fetal calf serum but did not inhibit concanavalin A-stimulated DNA synthesis of such cultured cells and, similarly, serum did not inhibit DNA synthesis of thymus cells cultured in the presence of fetal calf serum. The sera of all species examined were inhibitory except for fetal sera. As judged from a quantitative assay, bovine and porcine serum contained the highest titer of inhibitor, whereas sera from human, rat, mouse, and rabbit were clustered in a group exhibiting less inhibitor. Ascites fluid and lymph node extracellular fluids contained less inhibitor than found in the serum of the same animal and lysates of washed lymph node cells were devoid of inhibitor. Although fetal bovine serum and newborn bovine serum did not contain the inhibitor, it was detectable within 24 hours of parturition. The inhibitor is of relatively large apparent molecular weight (about 300,000) and has been purified about 70-fold.

Aging↗