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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adjuvant activity of a single highly purified saponin from the soap bark tree Quillaja saponaria was evaluated by using it as a component in an experimental vaccine containing rHIV-1 envelope protein (HIV-1 160D) adsorbed to alum. BALB/c mice immunized with experimental vaccine formulations containing the saponin adjuvant QS-21 produced significantly higher titers of antibodies than mice vaccinated with only the alum-adsorbed HIV-1 160D. Potent amnestic antibody responses to HIV-1 viral proteins were also induced. Ag-specific proliferative responses to recombinant proteins and to three variants of HIV-1 were significantly increased using QS-21 as an adjuvant. Alum-adsorbed HIV-1 160D failed to induce measurable proliferative responses to inactivated HIV-1 viruses, but group-specific proliferative responses were raised when the QS-21 adjuvant was used in the vaccine formulation. MHC class I restricted CTL specific for the immunodominant V-3 loop were induced but only when the QS-21 adjuvant was included in the vaccine formulation. The production of serine esterase by Ag-activated splenic mononuclear cells, indicating the maturation of precursor CTL, was used as a secondary measure of CTL activity, and this response was also increased. The specificity of antibody responses was not significantly broadened using QS-21; the adjuvant increased the immune recognition of epitopes throughout the HIV-1 glycoprotein 160. However, the specificity of the proliferation and serine esterase responses was broadened, suggesting that the QS-21 augmented cell-mediated immune responses specific for epitopes outside of the V-3 loop. Additionally, the QS-21 adjuvant appeared to induce recognition of weakly immunogenic epitopes that were not recognized using only alum-adsorbed HIV-1 160D. The ability of QS-21 to augment both antibody and cell-mediated immune responses suggests that this adjuvant could be a valuable component in subunit vaccines.
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PMID:Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. 153 34

Aluminum phthalocyanine tetrasulfonates (AIPcS) are photoactive compounds with absorption maxima at 665-675 nm. The inactivation of viruses (vesicular stomatitis virus, VSV; human immunodeficiency virus, HIV) added to either whole blood or red blood cell concentrates (RBCC) and platelet concentrates (PC) on treatment with tetrasulfonated AIPc (AIPcS4) was evaluated. Treatment of RBCC with 10 microM AIPcS4 and 44 J/cm2 visible light resulted in the inactivation of greater than or equal to 10(5.5) infectious doses (TCID50) of cell-free VSV, greater than or equal to 10(5.6) TCID50 of cell-associated VSV, and greater than or equal to 10(4.7) TCID50 of cell-free sindbis virus. Both greater than or equal to 10(4.2) TCID50 of cell-free and greater than or equal to 10(3.6) TCID50 of cell-associated forms of HIV were also shown to be inactivated. Encephalomyocarditis virus, used as a model for nonenveloped viruses, was not inactivated. Equivalent virus kill with Photofrin II required a substantially higher concentration of dye and longer exposure to visible light. Following AIPcS4 treatment, red cell integrity was well maintained as judged by the low level (less than 2%) of hemoglobin release immediately following treatment and on subsequent storage, by measurements of erythrocyte osmotic fragility, and by the normal recovery and circulatory survival on infusion of treated, autologous red blood cells in baboons. Treatment of PC with 10 microM AIPcS4 and 44 J/cm2 visible light also resulted in effective virus kill (greater than or equal to 10(5.5) TCID50) of VSV; however, both the rate and extent of platelet aggregation in response to collagen addition declined by at least 50%. Based on these results, further characterization of AIPcS4-treated RBCC is justified.
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PMID:Inactivation of viruses in red cell and platelet concentrates with aluminum phthalocyanine (AIPc) sulfonates. 161 88

The major envelope glycoprotein, gp120, of human immunodeficiency virus type 1 (HIV-1) was purified from a Chinese hamster ovary cell line transfected with a truncated form of the HIV-1 env gene. The recombinant glycoprotein (rgp120) was formulated with aluminum hydroxide adjuvant and was used to immunize chimpanzees. The recombinant preparation was effective in eliciting cellular and humoral immunity as well as immunologic memory. Anti-rgp 120 antibodies reacted with authentic viral gp120 in immunological blot assays and were able to neutralize HIV-1 infectivity in vitro. Sera from the rgp120-immunized animals were able to neutralize HIV-1 pseudotypes of vesicular stomatitis virus prepared from the IIIB isolate, from which the gene encoding rgp120 was derived, as well as two heterologous isolates, ARV-2 and RF. The immune response elicited against the rgp120 was not effective in preventing viral infection after intravenous challenge with HIV-1. The implications of these results on HIV-1 vaccine development are discussed.
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PMID:Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120. 245 98

The development of peptide-based vaccines that elicit antibody (Ab) and cellular immune responses has been hampered by the lack of highly immunogenic formulations. In this study, we compared the induction of Ab and cytotoxic T-lymphocyte (CTL) responses to a peptide derived from the V3 loop of HIV-1 gp120 (P18 and its cysteine-glycine derivative (CG-P18)) when incorporated into liposomes with lipid A (LA) or mixed with aluminum hydroxide. P18-specific CTL were only observed with liposomes with LA. P18-specific Ab responses were found with liposomes containing CG-P18 but not P18. Increased surface expression of the former, resulted in enhancement of the Ab response without loss of CTL induction. Thus, the manner in which a peptide is localized can influence the outcome of the response induced by highly immunogenic liposome formulations.
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PMID:Antibody and cytotoxic T-lymphocyte responses to a single liposome-associated peptide antigen. 749 19

The global HIV epidemic continues unchecked. Reports to the World Health Organization's Global Programme on AIDS indicate that more than 14 million persons have become infected with HIV and more than two million have died with AIDS. The spread of AIDS has generated a worldwide mandate for the development of safe and effective vaccines against HIV. Vaccines have been the most effective defense against other viral diseases such as polio and smallpox. However, the development of a vaccine against HIV-1 is a formidable task due to the variation of the virus, inadequate animal models of HIV disease, and the lack of correlates of protective immunity. Several candidate HIV vaccines are composed of synthetic, recombinant, or highly purified subunit antigens. Vaccines composed of subunit antigens generally are considered to be safer than traditional whole-killed or live-attenuated vaccines. However, purified subunit vaccines often are inherently less immunogenic than traditional vaccines. Immunologic adjuvants are agents that act generally to enhance specific immune responses to vaccine antigens. Formulation of experimental HIV vaccines with potent immunologic adjuvants is an attractive approach for amplifying and directing immune responses to highly purified antigens. Alum adjuvants, consisting of aluminum salts, first described in the 1920s, remain the only adjuvants in U.S.-licensed vaccine formulations. Novel adjuvants now undergoing preclinical and clinical testing with experimental subunit vaccine include detoxified lipid A, adjuvant emulsions, liposomes, biodegradable microspheres, muramyl peptides, and saponins. Adjuvants have been shown to elicit cytotoxic T-cell responses as well as antibody to subunit antigens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of adjuvants in retroviral vaccines. 765 11

T-cell adjuvancy involves the use of agents to stimulate preferentially delayed type hypersensitivity (DTH). Traditional adjuvants like Alum, Freunds, muramyl peptides, and endotoxins are not selective. Natural infection (e.g. vaccinia) may yield selective DTH. Low dose cyclophosphamide (CY) with mycobacteria was the first experimental T-cell adjuvant. New adjuvant formulations (ISCOMS, MAPS, etc.) with synthetic T-cell epitopes offer improved formulations. Upregulation of TH-1 helper cells and their actions with interleukins like IL-2, IL-12, and gamma IFN or antibodies to IL-4 and IL-10 may augment potently pathogen and tumor resistance. Similarly, transfection of tumor target cells with genes for IL-2, IL-12, gamma IFN, etc., offers novel vaccine treatment approaches. Finally, "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH responses. These approaches are seeing increasing emphasis in new treatment strategies for cancer and infections like HIV.
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PMID:T-cell adjuvants. 780 29

Cationic phthalocyanines with either aluminum or silicon as the central metal were evaluated for their ability to inactivate viruses in red blood cell concentrates (RBCC) photodynamically. In addition, the virucidal potential of a substituted anionic phthalocyanine, aluminum dibenzodisulfophthalocyanine hydroxide (A1N2SB2POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (A1PcS4OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitis virus (VSV), the virucidal potential of these phthalocyanines was: HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) = SiPc[OSi(CH3)2-(CH2)3N+(CH3)3I-]2 (Pc 6) > A1PcOSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I- (Pc 21) = A1N2SB2POH = A1PcS4 > HOSiPc[OSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I-]2 (Pc 14) > A1PcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 2). Phthalocyanine ligand 14 and Pc 21 are new phthalocyanines, made by quaternizing known amino analogues. Compared to VSV, the rate of inactivation of Sindbis virus (another model lipid-enveloped virus) was identical when treated in red blood cells (RBC) with Pc 5 and slightly higher when treated with Pc 6 and A1PcS4OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or A1PcS4OH required 15 min of irradiation to inactivate (> 5 log10 reduction) the virus. The extent of HIV-1 inactivation with A1N2SB2POH was 3.7 log10 after 60 min of red light exposure. The RBC integrity after photosensitization was measured by the ability of the cells to bind to plates coated with poly-L-lysine, (which reflects the retention of the RBC surface negative charges) and hemolysis of the cells over a 7 day storage period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New phthalocyanines for photodynamic virus inactivation in red blood cell concentrates. 793 15

Twenty-one cynomolgus monkeys were immunized with whole inactivated HIV-2 preparations administered with various adjuvants (incomplete Freund's adjuvant, Alum, Ribi, MDP, or Iscoms) and challenged with 10 or 100 MID50 of a homologous monkey-cell grown, cell-free HIV-2. Seven animals were completely protected against infection, three showed reduced virus replication. The vaccines elicited neutralizing and ADCC antibodies; the titers did not correlate with protection. Immunization with a whole inactivated vaccine can protect primates from intravenous challenge with a monkey-cell grown cell-free human immunodeficiency virus type 2.
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PMID:Efficacy of inactivated whole HIV-2 vaccines with various adjuvants in cynomolgus monkeys. 796 39

We have investigated the efficiency of a subunit vaccine consisting of native gp130 micelles of HIV-2ben mixed with keyhole limpet hemocyanin (KLH). Over a period of 52 weeks, nine cynomolgus monkeys (Macaca fascicularis) were immunized with seven intramuscular injections of gp130-KLH, equivalent to a total of about 1.1 mg of purified gp130 per animal. The first three applications were formulated in Freund's incomplete adjuvant. Because of the effects of Freund's incomplete adjuvant, aluminum hydroxide was used for the four subsequent immunizations. Each of the nine vaccinated animals along with six controls were challenged with 10 monkey infectious doses (MID50) of live HIV-2ben. At the time of challenge, the vaccinees had developed anti-gp130 titers ranging from 1 to 1.5 x 10(5). Four animals exhibited neutralizing antibodies. After iv challenge with 10 MID50 of HIV-2ben the nine vaccinees showed neither a secondary immune response nor a transient viremia. However, in four of the nine immunized animals proviral sequences were sporadically detected by polymerase chain reaction (PCR) and one of these four animals developed cytotoxic T lymphocytes. All six control animals developed a primary antibody response to HIV-2ben and became PCR positive. Four animals showed cytotoxic T cell activity and two developed a transient viremia. The five vaccinees with no sign of virus infection were reimmunized once and challenged with 10 MID50 of the heterologous virus HIV-2SBL-6999. Four weeks later all animals were PCR positive. A naive control animal and four of the vaccinees showed primary or secondary antibody responses and transient viremia. One of the revaccinated animals did not become viremic, and viral antibodies did not increase.
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PMID:Protection of cynomolgus macaques (Macaca fascicularis) against infection with the human immunodeficiency virus type 2 strain ben (HIV-2ben) by immunization with the virion-derived envelope glycoprotein gp130. 831 67

Even though the risks associated with the transfusion of blood products are lower than ever before, considerable efforts are being employed to improve the safety of the blood supply. Based upon available data, a six log (99.9999%) reduction in virus level from screened and tested blood components should significantly reduce or eliminate the risk of post-transfusion infection. The objective has been to identify "generic" methods, that is, one that would be applicable to all virus. For red cells, physical and chemical approaches have been studied; for platelets, the approaches have been limited to chemical. The physical methods include depletion of leukocytes by filtration, removal of plasma by washing, and viral inactivation by heat. Among the chemicals investigated to inactivate or help displace virus are ozone, detergents, and hypochlorous acid. Several photochemicals have also received intensive investigation: merocyanine 540, a benzoporphyrin derivative, aluminum phthalocyanine, and methylene blue. For platelets, photochemical inactivation methods using merocyanine 540, and two psoralen derivatives, 8-methoxypsoralen (8-MOP) and aminomethyl trimethyl psoralen (AMT), have also been studied. Approaches which include washing are not suitable. For the most part, either viral removal or inactivation has been insufficient, or red cell or platelet damage unacceptable. However, there are a few indications that at least inactivation of a specific virus, such as HIV, may be possible without major cell damage. These studies are in their early stages and significant work remains. If feasibility is clearly shown in vitro, it is likely that in vivo primate studies to demonstrate safety and efficacy will be required.
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PMID:Viral inactivation and reduction in cellular blood products. 847 92


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