Clinical trials involving 700 HIV-positive individuals haveshown that MicroGeneSys Inc.'s VaxSyn HIV-1 vaccine inducedantibody and cellular immune responses, company officials toldthe Eighth International Conference on AIDS, meeting inAmsterdam.

Data presented Tuesday were drawn from five independentstudies going back as far as 1989, but largely supportpreviously announced results from smaller clinical studies.

In other conference highlights, Applied Immune Sciences Inc.said Tuesday that, based on previously announced findingsconcerning its cell therapy for AIDS, it was ready to start PhaseII clinicals at San Francisco General Hospital. AIS officials saidthey anticipate commercialization "in the foreseeable future."

Other presentations were made by the University of California,San Francisco, Medical Center (UCSF); Harvard University; andthe Hospital de la Pitie in Paris.

In its report Tuesday, MicroGeneSys of Meriden, Conn.,presented data from recombinant pg160 vaccine.

In one study involving 30 asymptomatic HIV-infected patientstreated with VaxSyn at the Walter Reed Army Institute ofResearch, 97 percent developed notable vaccine-inducedantibody and cellular immune responses against HIV, thecompany said. The immune responses were not typically foundfollowing natural infection, and increased cellular immunity --both of which are thought to be important in combating HIVinfection.

"The clinical consequences will be delayed progression and/ordisease stabilization and prolonged survival," said principalinvestigator Robert R. Redfield, chief of the department ofretroviral research at Walter Reed in Washington, D.C.

The vaccine treatment stimulated new and heightened immuneresponses and reduced the rate of decline of the patients' T4cells. Group-specific responses were found not only to thevaccine strain, but to a broad range of other AIDS virus strains.

Similar results were reported from a study of 58 asymptomaticpatients by the National Institute of Allergies and InfectiousDiseases (NIAID) and the AIDS Clinical Trials Group. The studywas to determine if HIV-positive individuals showed the samedegree of improvement when their immune system is boostedby a vaccine not directed against HIV. Significant stabilizationoccurred in the percent of T4 cells of patients receiving VaxSyncompared with patients receiving the hepatitis B vaccine.Patients treated with VaxSyn displayed broadened HIV-specific antibody responses and increased activity of HIV-specific memory, helper and cytotoxic T lymphocytes.

A report of results from the first placebo-controlled studies ofthe gp160 vaccine, conducted by New York University andStanford University researchers, supports Redfield's findingsthat the vaccine is safe and stimulates the immune system ofasymptomatic healthy patients in the early stage of HIVinfection.

That New York University-Stanford group was sufficientlyencouraged by the results to start planning a large, multicenterclinical trials of the gp160 vaccine, which is being considered asan early intervention that may stimulate the body's attackagainst HIV soon after infection. Their aim is to extend thedisease-free period following the infection.

The Stanford group, which is comparing other AIDS vaccines, isencouraged by their finding involving the gp160 vaccine, butcautious because the disease can have a lengthy asymptomaticperiod of up to a decade.

"We are presenting our first-year analysis, which shows that itworks, but we have to see how long the immune-boostingeffect remains," said Stanford post-doctoral fellow SmritiKundu. "Gp160 is relatively inexpensive and non-toxic. So if itis effective, that would be really important for everybody."

A substudy conducted by Kundu examined the vaccine's effectson specific groups of immune system cells called cytotoxic TLymphocytes (CTLs). Exposing the T cells to infected targetcells, Kundu found that after the vaccine injections the T cells'ability to kill HIV-infected cells increases. "If we can increasethe HIV-specific CTL in the body, they will be able to recognizethose infected cells and eliminate them," he said.

In its report, Applied Immune Sciences said that in theupcoming Phase II trial, 20 Kaposi's sarcoma patients will betreated with five cell expansions and reinfusions over fivemonths, with a follow-up after three months.

"We should be ready to file for approval for our therapyprocess in under a year, assuming the data comes in aspositively as it has in the past," AIS spokesman Jerry Ford toldBioWorld.

"We see commercialization of our cell therapy in theforeseeable future," he said.

The Menlo Park, Calif., company reported on the safety andeffectiveness of expanded Phase I trials at the AIDS conference.

AIDS patients who received cell therapy in the Phase I trialsimproved from the most serious AIDS-related complications,including Kaposi's sarcoma, and recovered from others, thecompany said.

Cell therapy is used to reactivate dormant immune system cellsand make them grow to vastly increased numbers. Datacollected by Monto Ho and associates at the University ofPittsburgh, in collaboration with AIS, showed that CD8 cellsincreased from an average starting population of 540 million toas many as 11 billion. This may refute the prevailing viewamong scientists that even if a pure sample of CD8-positivecells could be obtained and grown in the laboratory, the cellswould die upon reinfusion or unable to function if theysurvived.

In other reports to the AIDS conference:

-- Whether an expectant HIV-infected mother will be amongthe 12 percent to 15 percent who transmit the infection totheir newborns might someday be determined by testing if herimmune serum helps or fails to inhibit virus from infectingwhite blood cells in culture. Women who transmit the virusduring pregnancy or childbirth are possibly infected by fast-replicating virus strains that are resistant to antibodiesproduced by the mother's immune systems, according toSrisakul C. Kliks, a UCSF research virologist.

-- Another UCSF study indicates voluntary and anonymoustesting for HIV infection gets a better response in states thatalso have in place anti-discrimination laws that restrict testingrequirements by prospective employers or insurancecompanies. States that require reporting of the names ofindividuals who test positive showed no significant differencein the level of testing from states that have no suchrequirement.

-- Harvard researchers have designed a molecule that invadesand incapacitates HIV virions that are sent out to invadehealthy cells. Zene Matsuda of the Harvard School of PublicHealth in Boston explained how he designed Virion-SpecificInterfering Molecules (VSIMs) for this purpose.

-- In another application of gene therapy for treating AIDS, theHospital de la Pitie in Paris succeeded in disrupting thereproduction of HIV by inserting a gene coded with a toxicprotein. This use of killer, or suicide genes, would still need tobe tested in mice and monkeys, according to Manuel Caruso, aresearcher at the hospital.

-- Michelle Slade Associate Editor

(c) 1997 American Health Consultants. All rights reserved.

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