WASHINGTON _ Genentech Inc.'s gp120 AIDS vaccine will betested in a Phase I safety and immunogenicity trial in 30 recoveringintravenous (IV) drug users in Bangkok, Thailand, beginning nextJanuary, according to officials at the World Health Organization(WHO). Jose Esparza, chief of the WHO's vaccine unit, toldBioWorld that investigators expect final clearance from the ThaiMinister of Health "any minute now."
The trial could jump-start clinical development of the vaccine, whichstalled last June when an advisory panel to the National Institute ofAllergy and Infectious Diseases (NIAID) voted against funding alarge Phase III efficacy trial in the U.S. If successful, the Phase I trialin Thailand could finally pave the way to a large-scale efficacy trialof gp120 vaccine _ a study that Genentech researchers haveactively promoted.
Genentech's vaccine is one of a class of recombinant subunit HIVenvelope-protein vaccines. The enormous genetic diversity of theAIDS virus and its continuing evolution has complicated the task ofdeveloping envelope vaccines and targeting the right populations inwhich to test them. The Genentech product is based on an HIV-1subtype B envelope, a subtype that infects about 50 percent of all IVdrug users in Bangkok, said Esparza.
The Biocine Company, a joint venture between Chiron Corp. andCiba-Geigy that has also developed a subtype B envelope vaccine,plans to develop and test a new gp120 vaccine based on subtype E,added Esparza. The new Biocine vaccine will be tested in northernThailand _ where subtype E is the prevalent subtype _ as aprotection against sexual transmission.
Although Genentech's and Biocine's gp120 vaccines have alreadyundergone extensive animal and human testing (at the Phase I and IIlevels) in the U.S., Esparza said that safety and immunogenicity needto be re-established in the exact population in which a future efficacytrial would be conducted.
Experts estimate that a Phase III efficacy trial in the Bangkokpopulation would ultimately need to enroll about 3,000 IV drug usersin order to produce statistically meaningful results. The Phase I trialof Genentech's vaccine set to begin next month will be conductedsolely by Thai investigators with "technical advice" from WHO. Itcould be completed within 12 to 18 months, said Esparza.
Esparza said that if the gp120 vaccine proves efficacious in theBangkok population, it will only be proven efficacious againstparenteral transmission of the virus (i.e., transmission via needles).Protection against parenteral transmission does not necessarilytranslate into protection against mucosal transmission. Thus a trial ina drug-user population would need to be repeated in a sexualtransmission population.
Last October, WHO consulted with a group of 34 internationalexperts to decide whether the organization should lend its support toefficacy trials of gp120 candidate vaccines in the wake of NIAID'srejection of the trials. (See BioWorld Today, June 20, 1994, p. 1.)Those experts concluded that although it's uncertain whether gp120vaccines will work, efficacy trials should be conducted.
"The decision of the National Institutes of Health [NIH] advisorycommittee created some problems for us," conceded Esparza. "Butthe NIH made it very clear that its decision applied only to the U.S.and not to countries where the epidemiology and status of the diseaseis very different."
Esparza pointed out that the higher rates of HIV-infection in developing countries such as Thailand make it moreurgent and more logistically feasible to conduct vaccine studies. Forexample, the incidence rate of HIV-infection among certain groups of homosexual men living in SanFrancisco is 2 to 3 percent per year, far lower than the rate among IVdrug users in Thailand, which is estimated to be as high as 7 percentper year in high-risk groups.
"These vaccines should be tested for three reasons," said Esparza."Number one, they may work. Number two, they may not be veryefficacious but what we learn may be important for the field of AIDSvaccine research. And number three, if they don't work we can rejectonce and for all the non-replicating recombinant subunit envelopevaccine hypothesis and move on to something else." n
-- Lisa Piercey Washington Editor
(c) 1997 American Health Consultants. All rights reserved.