There is a big meeting, at Gallo's Institute of Human Virology
A Symposium on HIV-AIDS & Cancer Biology
August 28-September 2, 1999 Baltimore, Maryland
ihv.org
"More than 130 researchers from nearly 20 countries are schedule to speak before an anticipated 1,000 attendees. Meeting topics include the latest research in: HIV pathogenesis and infection, vaccines, HIV structure-function, immune response to HIV, anti-HIV therapy, hepatitis viruses & their role in HIV, chemokines, HIV-1 & HHV-8 in Kaposi's sarcoma and lymphoma, cancer biology, suppressor genes, oncogenes, and tumor immunology / human viral carcinogenesis other than HHV8 (HTLV, HPV, EBV)."
The program is available at:
ihv.org
August 28th AIDS/HIV Infection & Pathogenesis
August 29th HIV/SIV Vaccines; HIV Structure-Function
August 30th Emerging Technologies
August 31st Immune Response to HIV & Pathogenesis, Anti-HIV Therapy, Hepatitis Viruses and their Role in HIV
September 1 Role of Chemokines in Development, Inflammation, and HIV Infection;
HIV-1 & HHV-8 in KS & Lymphoma
September 2 Oncogenes; Tumor Immunology; Human Viral Carcinogenses other than HHV8 (HTLV HPV EBV
Fred Valentine (#93) Ronald Moss IRC (#94) Bruce Walker (# 92) are speaking on August 31st.
Among the speakers: Robert Gallo, Anthony Fauci, Edward Berger, Judah Folkman; David Ho;
Douglas Richman; Robert Siliciano Mark Kaplan, Mark Goldsmith, Stephen O'Brien; Zvi Bentwich.Douglas Noonan; Mark Wainberg; Elisabetta Viani Puglisi; Ruth Ruprecht; Dan Bolognesi; Jack Nunberg; Warner Greene; Daniel Zagury; Brigitte Autran; Joepe lange;, Geoffrey Schiff;; Melchers; Eric Verdin; John Bartlett and many more
Roy Vagelos, from Regeneron (?)is co-chairman of one of the sessions.
A few of the presentations:
‹?ú "Host Factors in the Pathogenesis of HIV Disease," Anthony Fauci, National Institute of Allergy and Infectious Diseases
"Comments on some aspects of the future of (A) therapy of HIV and HIV disease and (B) on a preventive vaccine," Robert Gallo, Institute of Human Virology
‹?ú Daniel Zagury," University of Paris: "Tat Toxoid, a Safe and Immunogenic Component for a Preventive and Therapeutic AIDS Vaccine"
‹?ú Origin and Maintenance of the Latent Reservoir for HIV-1," Robert Siliciano, Johns Hopkins University
‹?ú Judah Folkman: Is there a molecular Connection between the Clotting System and Angiogenesis?
‹?ú Zvi Bentwich: Impaired Signal Transduction in Chronic Immune Activation. Relevance to the Pathogenesis of HIV Infection.
‹?ú Bruce Walker, "Effects of Early Therapy to HIV Specific Immune Response."
‹?ú Fred Valentine, "The induction of large Lymphocyte Proliferative Responses to HIV Antigens by the Administration of an HIV Vaccine to Subjects with Established infection"
‹?ú Ronald Moss (Immune Response Corporation) "HIV-1 Immune Recognition"
‹?ú Hana Golding, CDER/FDA Coreceptor Competition for Association with CD4 May Change the Susceptibilty of Human Cells to Infection with T-Tropic and M-Tropic HIV-1 Viruses
‹?ú Ethel Cesarman, Cornell: Central Role of VEGF-Recepptor 2 (KDR) in the Proliferation and Survival of Primary Human Endothelial Cells following infection by KSHV
‹?ú Jeffrey Schlom, NCI/NIH The Diversity of T-Cell Costimulation in the Induction of Anti-Tumor Immunity
‹?ú Ralph Reisfeld, Scripps : Cancer Immunotherapy with Immunocytokines
‹?ú Yoji Ikawa, Tokyo University: Human p53 Tumor Suppressor Gene Family and Their Chimeric Constructs for Gene Therapy
Here's a link to an abstract to be presented at ICAAC 1999
0691 Effect of HAART and Immune-Based Strategies in HIV-1-Infected Antiretroviral Naive Adults
asm.ctt-inc.com %257E%2560%253By
Free but you have to register first.
There was a comment on Yahoo that the results were better with IL-2 than with Remune, and both were better than HAART alone.
First, the abstract presents preliminary data for a small number of patients: 7 patients on HAART alone;
5 patients on HAART plus IL-2; and 6 patients on HAART plus Remune: hardly enough to show significance.
IL-2 and Remune are not really comparable, it's like comparing the function of protease inhibitor's to nukes.
IL-2 increases CD4 production. It is thought useful to activate resting infected immune cells, which then must be destroyed.
Remune stimulates the production of anti-HIV specific CTL's. It also lowers TNF, increases the production of IL-2 and other cytokines. It produces a strong anti HIV LPR.
It seems that effective immune control of HIV will require a combination of drugs that stimulate, inhibit and modulate various aspects of the immune system, just like effective HIV treatment requires a combination of drugs that work at different levels.
There was study presented at the last IHV meeting in 1998, summarized below:
prn.org
""Preliminary reports at the Annual Meeting of the Institute of Human Virology (1998) by Dr. Fauci and Dr. Joep Lange of the University of Amsterdam are promising. Dr. Fauciƒ??s team matched twelve patients with viral load titers below 50 copies/mL receiving IL-2 and HAART with 12 patients on HAART alone and viral loads below 50 copies/ml. Three of the patients receiving both IL-2 and HAARTƒ??as opposed to none of the patients on HAART aloneƒ??had no culturable virus and no latently infected lymphocytes could be detected in these patientsƒ?? peripheral blood using the same assay used by Dr. Siliciano (see above). Using an even more sensitive assay, no virus could be detected in 300 million white blood cells in two out of the three patients.""
Note that since these results were presented, the patients on IL-2 plus HAART were taken off HAART.
Within two to three weeks all the patients showed significant viral load increases, including the patients on IL-2 who had no detectable virus in the lymph nodes.
So just stimulating the production of CD4's is not enough.
Once HAART therapy resumed, they did become undetectable again.
Excerpts from Beyond 2000: A New Agenda for Management Strategies March 1999
prn.org
<In a plenary session at the 12th World AIDS Conference in Geneva, Dr. Ho outlined various management strategies, based on what is now knownƒ??and has yet to be learnedƒ??about the kinetics of HIV. On the whole, Dr. Ho did not view the presence of residual replication and the recalcitrant reservoir pessimistically. As Dr. Ho explained, eliminating residual replication may simply be a matter of modulating the intensity of HAART. Triple drug combinations and other combinations that are included in todayƒ??s cornucopia of available drugs are by no means a panacea. Recent studies have shown that four, five and even eight drug combinations appear to expedite virus decay in infected individuals faster than current therapies, and several new therapeutic agents are under study.
As for the reservoir of latently infected cells, perhaps immune activation might be utilized to purge these cells of HIV, thus speeding up the rate at which the recalcitrant reservoir is eliminated. Procedures for activating this latent pool of productively infected cellsƒ??for example, by using IL-2, GM-CSF, IL-12, OK3T mouse antibodies and/or therapeutic immunizationƒ??are currently being explored by a number of laboratories.
Dr. Lange reported similar results (results above by Dr. Fauci) in patients who were put on a regimen of five antiretrovirals, and treated with IL-2 and OK3T, a monoclonal mouse antibody that targets and activates T-lymphocytes vial the CD3 receptor. Clinically, this combination induced a condition similar to toxic shock. While the patients in this study became quite illƒ??and most were admitted to the hospital intensive care unitƒ??infectious virus could not be cultured from two of the three patients enrolled.
These results are only preliminary, and no patients have yet ceased therapy, but Dr. Fauci described himself as being cautiously optimistic. Other efforts are being made to increase specific immunity against the virus using HIV-1 Immunogen (Remune) and other vaccine candidates, perhaps altering antigen presentation to stimulate more effective host immune responses.
Overall, research continues to progress quickly in better understanding the process by which HIV is produced and destroyed in the body. Without this information, there can be no therapeutic advances. >
____________________
An older article, from March 1999 with more results with Remune
prn.org
Clinical Immunity to Opportunistic Infections and HIV
Michael Polis and Fred Valentine. In the PRN-Physicians Research Network
Also thought this was an interesting article from April 19, 1999 Note the reference to Jonas Salk.
Nobel Laureate Foresees CMI Vaccines
AIDSWEEKLY Plus; Daniel J. DeNoon, Senior Editor
(CW HENDERSON PUBLISHER www.newsfile.com) --
Vaccines that elicit cell mediated immunity (CMI) are on the way, predicted 1996 Nobel Prize winner Peter C. Doherty.
Doherty and colleague Rolf M. Zinkernagel jointly won medicine's top honor for their discovery that CMI responses are triggered by the T-cell recognition of foreign antigens in the context of the "self" molecules now known as major histocompatibility complex (MHC) antigens. They published the key findings of this work in 1974 (Nature, 1974;248:701-2 and Nature, 1974;251:547-8).
Now affiliated with St. Jude Children's Research Hospital, Memphis, Tennessee, Doherty is working with murine gamma-herpesvirus 68 (MHV-68). This virus establishes a lifelong latent infection in B lymphocytes. Recent studies - using a powerful new assay employing tetrameric MHC molecules loaded with viral peptides that bind and directly stain virus-specific effector and memory CD8(+) T cells - show that vaccination of MHV-68 infected mice with a vaccinia/MHV construct greatly enhances anti-MHV CMI responses. The advent of the tetrameric MHC assay recently revolutionized immunology by showing that the size of the specific CMI response to an invading virus is more than an order of magnitude greater than had previously been suspected (see Vaccine Weekly, April 4, 1998).
"In actual fact you can get a tremendous boosting effect in a chronic virus situation," Doherty said. "Now I find myself talking about post-exposure vaccines, which I never thought I would."
Doherty spoke in the keynote address to the Second Annual Conference on Vaccine Research, held March 28-30, 1999, in Bethesda, Maryland.
He noted that vaccine pioneer Jonas Salk had predicted this development, joking that "Back then I thought maybe he had gone around the bend." But the MHV experiments demonstrated that even in the context of a chronic infection, vaccination greatly boosts anti-MHV CMI.
"One might expect you would also see this happen in a tumor situation," Doherty said. However, he warned that HIV infection may not be as amenable to CMI vaccination alone because of the AIDS virus's extremely high rate of replication.
"In terms of HIV I think you want to be thinking in terms of all components of the immune system," he said.
Vaccines that elicit CD8(+) T-lymphocyte-mediated immune responses could also be employed as preventive vaccines. However, Doherty warned that the nature of secondary CMI responses predict that they will be better at preventing disease than at blocking infection.
"The CD8 secondary response may not be enough to prevent infection, but may be enough to prevent the lethal consequences of infection," he said. "This is the limitation of secondary CTL responses. Although they can get to the site of pathology more quickly, they have to be activated and they can only be activated in the lymph node - not at the site of pathology."
The Nobel laureate noted that vaccines have been made for all major pathogenic viruses susceptible to conventional approaches.
"What we are left with are the viruses that are doing something to the immune system," he said. "These are generally big viruses with lots of involvement with the host - not necessarily to kill but to proliferate." |
