It was hypothesized that immune recognition could be stimulated with combined immune-based and potent antiviral drug therapies. This study examined human immunodeficiency virus type 1 (HIV-1)-specific lymphocyte proliferation before and after treatment with an inactivated HIV-1 immunogen in 15 chronically infected HIV-1 seropositive subjects. Lymphocyte proliferation to the immunizing antigen (gp120-depleted HIV-1; P<.001), purified native p24 (P<.001), and recombinant p24 (P<.05) increased after treatment with the HIV-specific immune-based therapy. By HIV-1 antigen-specific flow cytometry, T helper CD4 lymphocytes, CD8 lymphocytes, and NK cells (all P<.001) were the predominant cell types proliferating in vitro after treatment. Additional phenotyping of proliferating cells revealed predominantly CD4 and CD8 memory (both P<.001) phenotypes. This study supports the concept that in vitro lymphocyte proliferation to HIV-1 antigens, augmented after treatment with an inactivated HIV-1 immunogen, involves primarily CD4 and CD8 cell memory immune responses.
The sixth component (C6) of complement was purified from human serum in fully hemolytically active form by a n t i 4 6 and anti-impurities immunoadsorbent column chromatography. When 3-4 L of p l e d normal human serum containing 10 mM EDTA as starting material was employed, the final C6 preparations exhibited yields ranging from 40% to 56% with 1780-1940-fold purification factors based on recovery of specific hemolytic activity. Highly purified C6 was found to be a relatively stable serum glycoprotein, containing 11.3% carbohydrate, that retained 80-100% functional hemolytic activity upon incubation under the following conditions: (1) 6 M guanidine hydrochloride or 6 M urea at 37 OC for 3 h, (2) 4 M potassium thiocyanate at 4 OC for 18 h, (3) 56 OC for 90 min, or (4) pH 5-11 at 37 OC for 2 h. C6 exhibited 4.7 p-(ch1oromercuri)benzoate (pCMB) and 6.3 DTNB [5,5'-dithiobis(2-nitrobenzoic acid)] binding sites per molecule; the C6 hemolytic activity was completely inhibited Complement ( c ) is a sequential, multimolecular system of plasma proteins which can be activated by a variety of immunological as well as nonimmunological stimuli (Muller-Eberhard, 1975). C activation, which can proceed via either the classical or alternative pathway, is mediated through a series of cascading reaction steps which are dependent upon the conversion of serum zymogens to active serine esterase enzymes. The classical C pathway is activated by IgG and IgM containing immune complexes and is composed of 11 plasma proteins which are identified numerically as C 1-C9 (Muller-Eberhard, 1969). The first component (Cl) is a calcium-dependent complex of three plasma proteins, C 1 q,
We examined the adjuvant effects of a synthetic CpG oligodeoxynucleotide immunostimulatory sequence (ISS) using a whole-killed, gp120-depleted HIV antigen (HIV-1 antigen) in a Lewis rat model. We hypothesized that HIV-1-specific CD4(+) T helper (Th) immune responses could be enhanced when an ISS was combined with an HIV-1 antigen in incomplete Freund's adjuvant (IFA). We also reasoned that if such Th responses were sufficient, such a combination might also induce HIV-specific CD8(+) T cell immune responses. Here we demonstrate that the HIV-1 antigen in IFA combined with ISS stimulates both CD4(+) and CD8(+) HIV-specific immune responses as measured by interferon-gamma (IFN-gamma) in the ELISPOT assay. A strong correlation between these CD4(+) and CD8(+) responses was demonstrated. Furthermore, we found that the HIV-1 antigen in IFA with ISS as an adjuvant stimulated strong antibody responses to core antigen (p24). These studies suggest that the combination of the whole-killed, gp120-depleted HIV-1 antigen in IFA with ISS may be an ideal candidate to test in nonhuman primates and in human studies as a preventive HIV-1 vaccine.
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