Studies of the immune response to the human immunodeficiency virus (HIV) have been hampered by the antigenic diversity of the HIV envelope protein. In an effort to predict the efficacy of vaccination we have compared the systemic antienvelope antibody response in seronegative volunteers immunized with recombinant gpl60 (either in vaccinia or as soluble protein produced in baculovirus) derived from the HTLV-IIIB strain of HIV-1 and in two laboratory workers accidentally infected with the same strain. 11 of 14 vaccinees responded to immunization by producing anti-gpl60 of similar titer and the same isotype as that seen in the laboratory workers. Four vaccinees also had antibody to the principal neutralizing domain (V3 loop) that was comparable in titer with that seen in the laboratory workers, but the fine specificity of anti-V3 antibody was qualitatively different in the two groups. Antibody that can block the interaction between CD4 and gpl20 was present at comparable levels in three vaccinees and the lab workers. Neutralizing antibody titers were markedly lower in the vaccinees than in the laboratory workers. In seven of the vaccinees, an immunodominant epitope was at amino acid 720-740. Analyses of monoclonal antibodies to this region indicate that they do not neutralize, bind to infected cells, nor function as immunotoxins. Although the anti-gpl60 antibody response was of similar magnitude in both infected and vaccinated individuals, there were important qualitative differences. (J. Clin. Invest. 1993.

Three laboratory workers have been infected with the IIIB

We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gpl60mB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before immunization, at the time of challenge with HIV, and at multiple time points in the 9 mo after challenge. Immunization resulted in a more rapid rise of antibody to gp160 in both high and low dose animals. Antibodies to the V3 loop induced upon infection were unaffected by immunization. In low dose animals, neutralizing antibody rose more rapidly and to higher levels in the immunized animals as compared with the control. There was no difference in neutralizing antibodies between immunized and control chimpanzees in the high dose group. Epitope mapping ofthe anti-gp160 response indicated that immunization with gp160 vaccinia induced a postinfection antibody response to a region of gp41 (amino acids 718-743) that was not immunogenic in control-vaccinated animals. These data indicate that failed vaccination with the HIV envelope can alter both the timing and epitope specificity of the subsequent anti-HIV antibody response. These studies also define the evolution and fine specificity of the antibody response during the critical period immediately postinfection. (J. Clin. Invest. 1994.

Earthworms are used as biomarkers to determine the bioavailability of contaminants. As such, their uptake of contaminants has been studied extensively. Protocols have been established to ensure that laboratory-obtained data are valid and comparable. However, the method of removing the organism’s gut content (depuration) before assessing the contaminant in the tissue is not standardized. The aim of this research project is to investigate some parameters for earthworm depuration: light conditions and coprophagy prevention. Eisenia fetida were depurated for 48 hours in two separate studies according to guidelines ASTM-E1676 and OECD Test No. 317. In one study, 2 frequencies of egesta removal were employed during depuration to prevent coprophagy and compared to the control (egesta and worms removed after 48 hours). In another study, the subjects and material egested were assessed under conditions of continuous darkness and the control (continuous light). The depuration methods that included egesta removal every 12 and 24 hours resulted in 62% and 10% more egested material per mg of earthworm than the control (filter paper disc change after 48 hours), respectively. The earthworms depurated in continuous darkness egested 94% more material per mg of earthworm than the control. The results indicate that depuration would be more total under continuous darkness and employing a coprophagy prevention method. These findings could lead to more efficient depuration methods.

No abstract