摘要:

The global human immunodeficiency virus type 1 (HIV-1) epidemic is devastating many communities and a well tolerated and effective vaccine is urgently required. Several lines of evidence suggest that vaccine-induced protective immunity can be achieved. This evidence includes individuals shown to have natural immunity, and the partially effective immune responses that are generated during natural infection. However, the obstacles to HIV-1 vaccine development are enormous. The only substantially effective vaccine studied in pathogenic animal models (live, attenuated vaccines) is at present far too unsafe. The only HIV-1 vaccine to proceed to efficacy trials (an envelope protein approach) has been disappointing in its immunogenicity and efficacy in preliminary trials. The antigenic variability of HIV-1 strains is also a great obstacle. Unfortunately, commercial realities also do not favour the expensive development of HIV-1 vaccines required most urgently in less developed countries. Despite these obstacles, there is cause for cautious optimism. Better tolerated HIV-1 vaccine approaches are currently showing great promise in primate models and preliminary clinical trials. Many governments and the World Bank are now providing the political will and funding necessary to fast-track HIV-1 vaccine development. Given sufficient long term scientific and commercial commitment to the HIV-1 vaccine development process, it is ultimately likely that a preventative HIV-1 vaccine will emerge.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All the drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for a full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&DInsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Two HIV-1 gp120 vaccines are under clinical development with Chiron Vaccines (Chiron). One study is being conducted in Thailand in collaboration with the Walter Reed Army Institute of Research (WRAIR) and is evaluating the immunogenicity and safety of 2 HIV-1 gp120 proteins derived from HIV-1 SF-2 (B strain) and the HIV-1 CM-235 ('Thai' E strain) in Chiron's proprietary adjuvant MF59. The second trial is a phase II trial, sponsored by the National Institutes of Health, also evaluating the safety and immunogenicity of a HIV-1 gp120 vaccine in MF59. Chiron also plans to participate in a ‘prime-boost’ phase I study in Thailand in collaboration with Pasteur-Mérieux Connaught and WRAIR shortly.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Wyeth-Lederle Vaccines-Malvern [formerly known as Apollon, a subsidiary of Wyeth-Ayerst (American Home Products)] in the US is developing a prophylactic vaccine against HIV-1 based on DNA encoding the HIV-1 envelope proteins and other nonstructural proteins. The vaccine is one of Wyeth-Lederle Vaccines-Malvern's Genevax products based on the direct injection of specific sequences of DNA.Genevax-HIV prophylactic vaccine consists of a bacterial plasmid containing 2 HIV genes encoding the viral envelope glycoproteins gp120 and gp41, together with a third gene, rev, which increases the expression of the 2 env genes. Researchers at the National Institutes of Allergy and Infectious Diseases are to evaluate the prophylactic efficacy of Wyeth-Lederle Vaccines-Malvern's Genevax-HIV in phase I/II trials in HIV-negative volunteers in the US.A second DNA construct being developed for prophylactic vaccination will contain genes encoded by the gag/pol region of the virus, which includes the core protein p24 plus certain enzymatic proteins.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Immuno AG's HIV MN gp160 vaccine is undergoing phase II clinical trials in Austria, Belgium, Denmark, Germany, Sweden and Switzerland, and phase I trials in the US.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Wyeth-Lederle Vaccines-Malvern (formerly Apollon), in collaboration with the University of Pennsylvania in the US, is developing a therapeutic AIDS vaccine using its Genevax technology. It is in phase I/II clinical trials in Switzerland (University Hospital, Zurich) and the US (University of Pennsylvania Medical Center). The vaccine consists of plasmid DNA encoding for HIV-1 gp160 envelope protein and 1 other nonstructural protein. It is hoped that the vaccine will induce an immune response and delay the onset of AIDS in asymptomatic HIV-infected patients.Wyeth-Lederle Vaccines-Malvern has also reported that another of their DNA vaccines has successfully protected 2 chimpanzees against HIV infection, making it the first published report to show efficacy of an AIDS vaccine in chimpanzees. The DNA-based vaccine included 2 different DNA plasmids, one encoding for the HIV-1 MN envelope glycoprotein gp160 and regulatory rev genes and the other plasmid encoding for the gag/pol structural genes (which code for the core protein p24) for the HIV-1 strain HXB2. Research was conducted at the University of Pennsylvania. It appears that Wyeth-Lederle Vaccine-Malvern licensed the DNA vaccine from the University of Pennsylvania.As part of this collaboration, Wyeth-Lederle Vaccines-Malvern will also test an experimental vaccine consisting of plasmid DNA encoding for the env, rev, gag and pol genes of HIV-1. The trial will combine standard antiretroviral therapy with the experimental vaccine in HIV-positive patients in an effort to eradicate the virus. The phase I trial will involve 21 patients and will be carried out under the leadership of Dr David Weiner.Wyeth-Lederle Vaccines and Pediatrics also appears to be collaborating with Chiron Corporation, Advanced BioScience Laboratories, Merck Research Laboratories and Basic Research Laboratory in the development of a vaccination regimen in chimpanzees involving priming with recombinant adenovirus-HIV1MN gp160 and boosting with HIV-1 SF-2 gp120.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Cel-Sci's HIV HGP-30W vaccine (HGP 30, HIV p17 vaccine) consists of a synthetic copy of a 30-mer peptide fragment of the gag-encoded p17 core protein from HIV-1 clade B viruses, attached to an immunogenic carrier, keyhole limpet haemocyanin, and administered with alum adjuvant. HGP-30W was chosen as a vaccine candidate because its sequence is highly conserved among different HIV strains and because it contains recognition sites for both T and B cell epitopes, thus having the potential to elicit both cellular and humoral immune responses. Use of the viral core protein was based on evidence that cell-to-cell transmission of the virus is the major mode of infection, rather than infection of cells by free virus particles. The vaccine has been shown to elicit immune responses to the major HIV-1 subtypes (A, B, C, D and E) prevalent in Africa, North America, Europe, India and Thailand. HGP-30W originated with Viral Technologies (a former joint venture between Cel-Sci and Alpha 1 Biomedicals which is now owned wholly by Cel-Sci).HGP 30 vaccine has completed 2 phase I clinical trials in high risk, HIV seronegative volunteers, in the UK and US. A further phase I/II clinical trial has been completed in the US in collaboration with the AIDS Research Alliance on 24 asymptomatic HIV infected volunteers. Following the positive results of these studies, the company and the AIDS Research Alliance were planning to test the vaccine in a phase I/II trial with Immunex's sargramostim.However, Cel-Sci may not continue development of its HIV HGP-30W vaccine in the US, instead shifting development to the Third World. The company appears to have terminated plans to conduct phase II trials in Zambia with an improved version of HGP 30, due to difficulties in obtaining authorisation from the Zambian government. Cel-Sci now intends to begin a clinical trial in southern Africa sometime in 1999. Meanwhile, the company is conducting a phase II study in 30 healthy HIV-negative volunteers in the Netherlands to generate critical dose response information useful for future trials. HIV-negative volunteers at the Institute for Clinical Pharmacology, Pharma Bio Research, in the Netherlands will receive 1 of 3 different dosages of HGP-30W.HIV HGP-30W is available for licensing worldwide. Cel-Sci has reacquired licensing rights from Nippon Zeon of Japan to develop and market the vaccine in the Pacific basin countries.Cel-Sci Corporation has announced that Dr. J. Talmadge at the University of Nebraska Medical Center in Omaha, Nebraska, USA, has received a grant from the National Institutes of Health to evaluate several forms of Cel-Sci's HGP-30W AIDS vaccine antigen in mice together with new cytokines supplied by Immunex Corporation.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

VaxGen has received approval from the US Food and Drug Administration and Thailand's Ministry of Publich Health for phase III trials of its bivalent, prophylactic vaccines for HIV, AIDSVAXTMB/B' and AIDSVAXTMB/E, respectively.The phase III trial in the US and Canada (40 clinical sites) is involving 5000 HIV-negative volunteers who are risk of sexual transmission of HIV. The trial marks the first time that an HIV vaccine will be evaluated in a large-scale prevention study in humans in the US. AIDSVAXTMB/B' consists of alum adjuvant with recombinant gp120 proteins from 2 clade B HIV-1 viruses, HIV-1 MN and HIV-1 GNE8, a T cell tropic virus and a macrophage tropic virus, respectively. These 2 HIV-1 strains have complementary neutralisation sites. Clade B viruses are the predominant strain of HIV-1 circulating in North America, Western Europe, Australia, the Caribbean, parts of Thailand and South America.The multicentre (17 clinics) Thai trial will involve approximately 2500 volunteers at high risk of HIV infection because of injectable drug use. AIDSVAXTMB/E is designed to protect against strains of HIV-1 prevalent in Thailand, Korea, Japan, Taiwan and Indonesia.There is controversy within the AIDS research community regarding gp120-based vaccines in general and specifically the progression of AIDSVAXTMto phase III testing. A number of scientists have argued that based on the lack of efficacy of the vaccine in phase II trials, it is unlikely to provide any prophylactic benefit. These researchers also pointed to a number of cases in which volunteers who received a gp120-based vaccine later became infected with HIV-1, with no significant immunological differences existing between these individuals and those who did not become infected. This suggested that the vaccine provided no protective efficacy. However, Donald Francis, the president of VaxGen, has responded by pointing out that phase I and II clinical studies are not designed to demonstrate efficacy and that statistical evidence regarding the efficacy of AIDSVAXTMcan only be be gathered by employing the sample size provided for by phase III studies. Furthermore, he commented that individuals with breakthrough HIV-1 infections which occurred during clinical studies with gp120-based vaccines were all infected by viruses whose gp120 proteins were structurally distinct from that used in the vaccines. Therefore, he stated that it is possible that gp120 vaccines may be effective if they include gp120 proteins from more than 1 HIV strain, as does AIDSVAXTM.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

vCP205 is an HIV-1 vaccine consisting of a live recombinant canarypox virus containing the following HIV-1 genes: gp120 (HIV-1MN) and the gp41 transmembrane region (HIV-1LA1) of env, gag (HIV-1LA1), and a portion of pol (HIV-1LA1) sufficient to encode protease activity. The canarypox virus cannot replicate in human cells and functions as a vector for the insertion and expression of these genes, which encode proteins known to elicit immune responses against HIV-1, by inducing the production of pseudovirions (non-infectious HIV-like particles).vCP205 has been tested in over 700 volunteers in AIDS Vaccine Evaluation Group (AVEG) protocols and an injectable form is currently being assessed in a US phase II trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Ongoing phase I trials are investigating mucosal delivery of vCP205 and IM delivery with a novel adjuvant, Immunex's granulocyte macrophage colony stimulating factor, hoped to boost the immune response more than the traditionally used alum.Pasteur Mérieux Connaught (Rhône-Poulenc Group, France) and NIAID announced on February 9 1999 that the first AIDS vaccine trial in Africa had begun in Uganda. This double-blind phase I trial, known as HIVNET 007, will enroll 40 healthy, HIV-negative adults aged 18 to 40 years who are in low risk categories for HIV-1 infection. The volunteers will be randomised to receive HIV vaccine vCP205, placebo or canarypox rabies vaccine. Volunteers will receive 4 doses over 6 months and will bemonitored over a 1-year study periodwith an additional year of follow-up to monitor safety. The induction of cellular immune responses directed against cells infected with HIV-1, specifically CD8+ cytotoxic T lymphocytes (CTL), and humoral immune responses (neutralising antibodies) directed specifically against HIV-1, will be monitored. The HIV-1 genes in the vCP205 vaccine originate from clade B viruses only, the predominant subtype of HIV-1 found in the US and Europe. However, the researchers will look for immune responses to clades A and D, as well as clade B, because the former 2 subtypes cause most HIV-1 infections in Uganda.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Although currently available lipid lowering therapies are effective and well tolerated, the search continues for additional treatments with even better efficacy and tolerability profiles. As well as refinements to existing strategies (new HMG-CoA reductase inhibitors, fibrates and combination therapies) new avenues are being explored. These include inhibitors of enzymes other than HMG-CoA reductase involved in cholesterol regulation and drugs which affect absorption of lipids from the gastrointestinal tract. In the case of the latter, it has been shown that the new antiobesity treatment orlistat can favourably affect the blood lipid profile. In line with an increasing emphasis on improving high density lipoprotein-cholesterol (HDL-C) levels, the potential therapeutic roles of niacin and drugs which inhibit enzymes involved in the metabolism of HDL-C are also being researched.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS