The Bay Area Reporter - May 15, 1998
Bill Snow, ACT UP/Golden Gate Writers Pool

The Phase II trial enrolled fully by the end of 1997 and is contributing important data for moving forward. But the road of science, and industry, seldom runs straight. In the meantime, PMC has made what it thinks are two improvements in its ALVAC vaccine. The company has added another HIV gene (nef) to the genes that were in vCP205 (gag, part of pol, and part of env) creating vCP1433, and added some coding sequences from another virus (vaccinia) to improve the expression of ALVAC in human cells, in vCP1452. PMC likes this last construct best, because it believes it is the best it can do with the ALVAC canarypox vector, and because vCP1452 will be easier to produce in large quantities. Of course the proof will be in the testing; a previous "improvement," vCP300, was a washout last year.

So the company, with cooperation from the AIDS Vaccine Evaluation Group (AVEG), has decided to delay production of vaccine for an efficacy or proof of concept trial until the two new ALVACs can be compared against vCP205 in a new Phase I trial. This kind of delay for companies to improve products is not unfamiliar in drug development, but it does push out the dates for testing this concept. The new Phase I comparison trial, AVEG034, should begin enrollment this summer, with data to allow choice of an ALVAC product by early 1999.

Unfortunately, PMC won't begin production of enough vaccine for an efficacy or proof of concept trial until this decision is made, and it predicts production of manufacturing grade vaccine will take about a year. This means a government sponsored efficacy trial is pushed into the year 2000. Or later.

Pushing the envelope

This delay and ongoing research into HIV envelope and antibody has also raised questions about the second part of the combination. Chiron has also been moving ahead with more advanced concepts. That company has decided that its SF-2 rgp120 in the current Phase II trial probably has little or no prospect to become a commercial product, because of what we've learned in the meantime about the virus and antibody. Since it would cost Chiron many millions of dollars to produce this old rgp120 for a large trial, it is instead moving ahead in Thailand with a combination envelope vaccine that includes a local Thai strain of wild type virus, which current thinking considers more promising for a useful antibody.

This is the same approach VaxGen is taking with its domestic and Thai gp120s (see "VaxGen: Pushing the Envelope," in this column in January). Chiron is also moving ahead with some other approaches besides envelope proteins.

The ALVAC delay and Chiron's reluctance to participate and redirection has made it likely that another, theoretically better, envelope vaccine will be needed in time for the now delayed ALVAC trial. At present the two most likely alternatives are a wildtype rgp160 that PMC is making itself and the VaxGen double strain (bivalent) gp120. Clearly PMC would be happy to have two of its own products in trials together, but its gp160 is early in development and presents additional problems that need to be ironed out, by making it harder to distinguish vaccine-induced antibody from actual infection. The PMC rgp160 will be used in the three-month and six-month boost of the three canarypox constructs in AVEG 034, and the VaxGen AIDSVAX will probably be added to the ALVAC-only arm of the ongoing Phase II trial.

This means that there should be at least some data within the next year to identify two products for the U.S. government's first long-discussed and long-awaited efficacy trial. The government trials networks, after years of talk and vaccine preparedness, are beginning to let its investigators begin designing trials for the millennium.

Meanwhile, VaxGen is moving ahead, setting up a private trial of its new gp120 tp test the concept of antibody alone in the U.S. and Thailand. The company is currently refining a protocol and identifying sites; San Francisco is likely to be one of them.

Good words, little action

Last week saw the first anniversary of President Clinton's challenge to develop a preventive vaccine in a decade. Mayor Brown issued a proclamation and honored local volunteers, companies, and even a vaccine advocate. This was an altogether upbeat affair. On the Friday before, the AIDS Vaccine Advocacy Coalition (AVAC) issued its more critical report, Nine Years and Counting: Will we have an HIV vaccine by 2007?

The message from AVAC is that it has been a year of good words and not enough action. Agencies funded to conduct HIV vaccine research and development must establish clearer plans and goals to expand the vaccine pipeline. The U.S. Government must be clear about who should take responsibility and accountability to achieve these goals. Increased commitment, funding, and courage is required from all sectors. The report states that at the current level of effort we will not meet the ten-year goal and that the logical answer is to do many things at once in a clearly planned effort.

The AVAC report can be found online at http://www.vaccineadvocates.org. So, enjoy the summer, there's no crowds and not much activity on vaccine beach. Anybody want to scream?
980515
BR980503

Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .