Search PubMed⌕ Search

Biomedical subjects

R C Kennedy

Publications and source records attributed to R C Kennedy.

At least 145 records · Page 8Linked to original sources
PubMed1986

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↗
PubMed1986

The detection of a common idiotype of anti-DNA antibodies in the sera of patients with monoclonal gammopathies.

The sera of 265 patients with monoclonal gammopathies were examined for the presence of a dominant idiotype of the anti-DNA antibody [16/6 idiotype (Id)] and for anti-DNA activity. An enzyme-linked immunosorbent assay (ELISA) with a rabbit anti-16/6 antibody revealed 23 (8.7%) sera that contained increased concentrations of the idiotype. Seven of the patients had benign monoclonal gammopathy, three multiple myeloma, three Waldenström macroglobulinemia, five essential mixed cryoglobulinemia, and five monoclonal cryoglobulinemia. In 5 of the 23 sera, antinuclear activity was also noted. In 11 of the 16/6 Id-positive sera the anti-nucleic acid antibody reactions were found to be polyspecific, reacting with polydeoxythymidilic acid and polyinosinic acid, in addition to single-stranded DNA and double-stranded DNA. Similar results were achieved with the purified serum monoclonal components. The specificity of the idiotype analysis was demonstrated with an unrelated dominant idiotype of anti-HBsAg antibody. In none of the patients, except one (with essential mixed cryoglobulinemia), was lupus symptomatology noted.

Antibodies, Anti-Idiotypic↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Temporal replication of the Pullman strain of Aleutian disease virus in royal pastel mink.

Information was sought on the temporal replication of Aleutian disease virus in 27 royal pastel mink. Groups of three were examined 8 to 126 days after they were inoculated subcutaneously with 10(3) 50% lethal doses of the Pullman strain. Much individual variation was noted in the onset of infection, occurrence of viremia, and extent of virus replication in the tissues. Thus, virus was detected in lymph nodes regional to the site of inoculation in only some mink during the first 14 days after inoculation. During this period, virus was often present as well in the mesenteric lymph node and spleen. First detected on day 10, viremia was present in all mink examined on day 28 but occurred irregularly thereafter, even when virus was widespread in the tissues. Except in five mink succumbing to the disease, the tissue distribution of virus after day 28 tended to be more limited, and the titers were generally lower than they had been earlier. Even though present in the lymph nodes and spleen, virus was often absent from the kidney, liver, and intestine after day 28. Specific antibody was detected on day 28 and was present in all mink thereafter, ostensibly without any adverse effect on virus replication. In most mink, the infection was considered subclinical, for it was usually not accompanied by a rise in serum gamma globulin or by morphologic evidence of the disease. The virologic findings in this study have a bearing on the relationship of subclinical infections to both horizontal and vertical transmission of the virus.

Aleutian Mink Disease Virus↗
PubMed1984

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↗
PubMed1984

Antibody to hepatitis B virus induced by injecting antibodies to the idiotype.

Anti-idiotype reagents that recognize a common idiotype associated with antibody to hepatitis B surface antigen (anti-HBs) were used to induce anti-HBs in mice. The anti-idiotype-induced anti-HBs was found to recognize the group-specific a determinant of hepatitis B surface antigen and to express an interspecies idiotype. These findings suggest that anti-idiotypes may be useful as vaccines or vaccine primers.

Animals↗
PubMed1984

Enhancement of the immune response to hepatitis B surface antigen. In vivo administration of antiidiotype induces anti-HBs that expresses a similar idiotype.

BALB/c mice receiving antiidiotype antibodies before the injection of hepatitis B surface antigen (HBsAg) generated an enhanced anti-HBs response. Mice given antiidiotype antibodies in a soluble form induced predominantly IgM anti-HBs, whereas alum-precipitated antiidiotype produced primarily IgG anti-HBs. Injection of antiidiotype antibodies alone induced anti-HBs that inhibited a common interspecies anti-HBs idiotype-antiidiotype reaction and recognized the group-specific determinant of HBsAg. These data support the view that antiidiotype antibodies may modulate the immune response to an infectious viral agent.

Animals↗