The World Health Organization (WHO) has approved large-scaletrials of potential HIV vaccines _ even though there may be lowefficacy rates _ in developing countries, with Thailand a likely firstsite.Representatives of half a dozen companies developing HIV vaccinessat down last month in Geneva with 27 AIDS experts from ninecountries. The WHO Global Program on AIDS had convened this adhoc committee to discuss "Scientific and public health rationale forHIV vaccine efficacy trials."The current issue of The Lancet reported this two-day meeting (Oct.13-14) in a brief news item headlined, "Go-ahead for HIV vaccinetrial in developing world."One American participant was Margaret Johnston, acting deputydirector of the AIDS division at the National Institute of Allergy andInfectious Diseases (NIAID). She told BioWorld Today that "thepurpose of the meeting was to evaluate the current developmentstatus of the recombinant glycoprotein 120 vaccine products, andlook _ at a global level _ at whether large-scale efficacy trials ofthat concept, as distinct from any specific product, should go ahead."In a press statement following the two-day gathering, WHO's GlobalAIDS program said that the committee "concluded that large-scaletrials [Phase III] of some candidate vaccines could go ahead toestablish if they can protect people from HIV infection."From Could, To Should, To WillJohnston said, "That conclusion didn't say `should' it didn't say`will' it said `could.' Getting from could to will," she continued, "isgoing to take looking at specific protocols proposed by specificcountries, and more specific issues about those protocols, before theWHO will say: `We actually will do a trial.'"This WHO advisory panel was different from NIAID's AIDSadvisory committee meeting last June, which recommendeddeferring sine die large-scale efficacy trials of candidate vaccines.(See BioWorld Today, June 1, 1993, p. 1.) "What distinguished theWHO panel from NIAID's meeting and decision," Johnstonexplained, "was that WHO took into consideration not only thescientific results, but also the general dynamic of the epidemicworldwide."Lancet's news item cited Oxford University epidemiologist RoyAnderson, who told the Geneva meeting that "even a low rate ofefficacy would be of significant benefit in developing countries . . .even if the candidate vaccines had an efficacy rate as low as 30 or 50percent, and provided protection for only up to five years."To which Johnston commented, "The efficacy rate of those candidatevaccines is entirely unknown. That's why you do efficacy trials."Will gp120 Protect Homo Sapiens?South San Francisco-based Genentech Inc.'s AIDS vaccine projectleader, Donald Francis, concurred. Having protected 100 percent offive chimpanzees challenged with his recombinant gp120, he toldBioWorld, "Traditionally, in vaccine development, this is where weget out of the test tube and animal stuff, and into humans. We'vegiven our vaccine to 1,000 people, and it looks very safe." Sideeffects? "Sore arms in about 20 percent, which is what you expect."Francis said that, "Only two companies have advanced from Phase Ito Phase II clinical trials, Biocine [a Chiron/Ciba-Geigy jointventure] and ourselves." Both were among the six vaccinemanufacturers attending the WHO gathering.Well before that event, Francis added, Genentech had been invitedby WHO and Thai scientists and authorities to discuss an efficacytrial in Thailand. He said, "Having the WHO approve the moving ofthese vaccines ahead is important to continuing our work inThailand.Biocine's AIDS vaccine specialist, Anne Marie Duliege, with whomGenentech's Francis has "worked very closely," is also exploringcollaboration with Thailand as a test-bed for her company'srecombinant gp120 vaccine.That Southeast Asian country, the size of California plus SouthCarolina, has an estimated population of 55 million. No firmstatistics exist as to the prevalence of AIDS. A WHO report haspartial estimates: Among military recruits age 21, 3.5 percent areinfected countrywide, but in the northern part of the country, recruitprevalence runs close to 20 percent.In all of South and Southeast Asia, the report estimates total HIVinfection at more than 2.5 million people, and actual symptomaticAIDS cases at 250,000. WHO notes that 90 percent of all newinfections occurs in developing countries.Genentech's partner in Thailand is Sricharoen Migasena, who directsthe country's AIDS vaccine trial center. She also teaches clinicaltropical medicine at Mahidol University in Bangkok.Lancet quoted her prediction that Phase I and Phase II trials forimmunogenicity and safety "could start as early as next month[November]." She added, "Only if these give satisfactory results willPhase III trials be conducted."Francis foresees that start-up as beginning "in the next severalmonths," and that the Phase I/II studies will "take a full year,"leading up to the full-scale efficacy program.NIAID's Johnston reckons that such an efficacy trial would requirethree to five years. Then, "if it proved efficacious in Thailand, thatwould certainly have impact elsewhere in the world." n

-- David N. Leff Science Editor

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