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Biomedical subjects

G Gorse

Publications and source records attributed to G Gorse.

8 recordsLinked to original sources
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed1998

Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group.

Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8+ cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection. Recombinant envelope proteins induce NAs but rarely CD8+ CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8+ cytotoxicity but few NAs. To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160LAI and boosting with recombinant gp120SF-2, gp120LAI, gp120MN, or gp160MN. Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL. Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies. Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months. Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy.

AIDS Vaccines↗
PubMed1997

Genetic and immunologic characterization of viruses infecting MN-rgp120-vaccinated volunteers.

Proviral sequences were determined and immunologic characterization was carried out for envelope glycoproteins from 7 vaccinees who became infected with human immunodeficiency virus type 1 (HIV-1), through high-risk behavior, while participating in clinical trials of MN-rgp120, a candidate HIV-1 vaccine. All 7 infections resulted from subtype B viruses; however, only 3 of the viruses possessed the MN serotype-defining V3 domain sequence, IGPGRAF, prevalent in 60%-70% of US infections. Six of the 7 viruses differed from MN-rgp120 at a neutralizing epitope in the C4 domain, and all 7 differed from MN-rgp120 at a neutralizing epitope in the V2 domain. Recombinant gp120 was prepared from each breakthrough specimen and tested for binding to a panel of neutralizing monoclonal antibodies. The results suggest that 6 of 7 breakthrough infections may be related to incomplete immunization or to infection with viruses that differed from the vaccine immunogen at important virus-neutralizing epitopes.

AIDS Vaccines↗
PubMed1994

Comparison of the immune response to recombinant gp120 in humans and chimpanzees.

OBJECTIVE: To assess similarities and differences in antibody responses to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial. METHODS: Frozen sera from humans immunized with rgp120 from HIV-1IIIB and chimpanzees immunized with the same antigen or recombinant soluble gp160 were compared in a variety of serologic assays. RESULTS: The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the antibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp120 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp120 was higher in the sera from the immunized chimpanzees than in the immunized humans. CONCLUSIONS: While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.

AIDS Vaccines↗
PubMed1993

Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine.

A recombinant human immunodeficiency virus 1 IIIB (HIV-1IIIB) gp120 subunit vaccine (IIIB-rgp120/HIV-1, Genentech) was tested for safety and immunogenicity in a randomised, double-blind, placebo-controlled phase-I trial. HIV-1-seronegative adult volunteers received three 100 micrograms or 300 micrograms doses of IIIB-rgp120/HIV-1 in alum adjuvant (10 vaccinees in each group), or alum adjuvant alone (8 vaccinees), at 0, 4, and 32 weeks by intramuscular injection. The three injections were well tolerated in both vaccine groups. Antibodies that neutralised homologous HIV-1IIIB were induced in 9 of 10 recipients after three 300 micrograms doses, and 6 of these 9 sera also neutralised heterologous HIV-1SF2. A dose response was evident, since three 100 micrograms injections induced lower titres of HIV-1IIIB neutralising antibodies and in fewer recipients (5 of 9) than the higher dose, with no neutralisation of HIV-1SF2. Similarly, syncytia-inhibiting, CD4-rgp120-blocking, and HIV-1IIIB V3-binding antibodies were induced in a dose dependent manner. Response to the 300 micrograms per dose vaccination occurred in a larger proportion of volunteers and at higher mean titres than seen in previous human trials with other recombinant envelope subunit vaccines or live vaccinia-env priming followed by envelope subunit boosting.

AIDS Vaccines↗
PubMed1986

The effect of hydrocortisone on the production of gamma-interferon and other lymphokines by human peripheral blood mononuclear cells.

Concentrations of hydrocortisone as low as 0.08 microgram/ml significantly reduced the yields of gamma-interferon (IFN-gamma) when phytohemagglutinin (PHA) or concanavalin A (ConA) were used as inducers; however, when staphylococcal enterotoxin A was utilized, higher concentrations (5.0 micrograms/ml) were required to achieve the same effect. Yields of interleukin-2 (IL-2) and lymphotoxin were also found to be sensitive to the effects of the steroids, but expressions of TAC antigen was not generally affected by these agents. In contrast to the effects of steroids on cell proliferation, lymphokine production remained suppressed after steroid withdrawal. Hydrocortisone appeared to influence the concentrations of cyclic nucleotides following lectin stimulation, but attempts to correct these alterations or to add exogenous IL-2 failed to restore lymphokine production to normal levels. Addition of the calcium ionophore A23187 partially restored IFN-gamma production. We conclude that the effects of corticosteroids on the yields of lymphokines, including IFN-gamma, are profound. The depression of lymphokine production appears to be associated with a number of alterations in the cell, including depression of protein synthesis, alterations in cyclic nucleotides, and diminution of the production of cofactors necessary for IFN-gamma production. Enhancement of the flux of calcium into the cell may restore some of the ability to produce IFN-gamma.

Antigens, Surface↗