ASU joins effort to accelerate HIV vaccine

ASU's Biodesign Institute will embark on an international collaboration with Switzerland's Centre Hospitalier Universitaire Vaudois (CHUV) in an effort to ramp up the production pipeline of new HIV vaccine candidates for clinical trials.

It has been 25 years since the first cases of AIDS, the acquired immune deficiency syndrome, were first reported. Since that time, more than 40 million individuals have been infected by HIV in the worldwide viral pandemic. Despite many vaccine candidates that have been tested – and the progress in HIV research – an AIDS vaccine has remained an elusive goal.

As a result, a new, $287 million network of international research consortia involving 165 investigators from 19 countries has been assembled in the hopes of breaking through the AIDS vaccine development logjam. One such research team – Poxvirus T Cell Vaccine Discovery Consortium (PTVDC) – is led by CHUV, including 14 institutions and companies from Australia, Canada, France, Germany, the Netherlands, Spain, Switzerland, the United Kingdom and the United States.

CHUV lead investigator Giuseppe Pantaleo has been awarded a five-year, $15.3 million grant, one of 16 awards from the Bill & Melinda Gates Foundation, to create a research center devoted toward enlisting poxviruses in the global fight against HIV (the human immunodeficiency virus) and AIDS.

“Protective vaccines against a variety of infectious agents represent one of the most significant achievements of biomedical research during the 20th century,” Pantaleo says. “Yet no efficient vaccine exists against one of today's major infectious threats: HIV/AIDS. PTVDC is committed to collaborate with other initiatives of the Global HIV Vaccine Enterprise to increase the probability of success, and to ensure global access – particularly for the developing world – once a successful HIV vaccine is developed.”

ASU School of Life Sciences professor and pox virus expert Bertram Jacobs will play a pivotal role in the CHUV team effort, with a $900,000 research project to genetically engineer pox viruses to ward off HIV infection.

“Making an HIV vaccine is an incredibly daunting task,” says Jacobs, a researcher in the Center for Infectious Diseases and Vaccinology within the Biodesign Institute. “But we've got some of the best people in their respective fields working together on this project.”

Jacobs is one of the world's foremost experts on a pox virus called vaccinia, a cousin of the smallpox virus. Vaccinia virus first was used to eradicate smallpox. Now the research team wants to attempt a similar fate with HIV.

For the past 20 years at ASU, Jacobs has conducted basic research with the vaccinia virus. Jacobs has more than $3 million in federal research funding for projects that include producing a safer smallpox vaccine and a post-exposure vaccine to counter a bioterrorism incident.

“We are now taking the same technology that we are proposing to make a safer, better smallpox vaccine and using that technology to try to make a vaccine that will work against HIV,” says Jacobs, leader of an ASU team that includes assistant research professor Karen Kibler as co-investigator and a team of 20 undergraduate, graduate and post-doctoral researchers.

The road linking vaccinia together with HIV research may not seem inherently obvious, but for Jacobs it began with a trip he made a half-decade ago, when he attended his first international AIDS conference in Durban, Africa, in 2000.

“That's when I got my first idea of what the AIDS epidemic was really like in Africa,” Jacobs says. “When I went to that meeting, I made a commitment that we would try to use our technology to fight the epidemic. So, for me, this has been a long time coming – and now we are going to be able to test whether our technology will work.”

Sub-Saharan Africa has been especially hard hit by the AIDS epidemic, containing the majority (25.8 million) of the world's estimated 40 million cases of HIV. By comparison, there are 1.2 million cases in North America .

In the project, novel vaccinia vectors, or “carrier viruses” – batches of genetically altered vaccinia virus – will shuttle in different combinations of HIV genes to trigger a protective cellular, or T-cell mediated, immune response.

“You can think of it as a vaccinia virus ‘ship' to deliver the HIV cargo,” Jacobs says. “As the body's immune system is fighting the vaccinia virus, it will also be fighting the HIV proteins that are part of the cargo that is going in with the vaccinia vector.”

The use of pox virus-based vaccines is supported by extensive preclinical and clinical experience (one of the pox viruses that will be used is a modified version of the vaccinia virus that was used to eradicate smallpox), and evidence suggests that pox virus vector vaccines could be significantly improved in their ability to stimulate cellular immune responses.

“We've got a vaccinia virus that makes a better immune response and by putting the HIV genes in, we hope it will make a better immune response to HIV,” Jacobs says.

The consortium will focus on making improvements to three pox virus vectors that have been used in HIV vaccines: MVA, NYVAC and ALVAC. The investigators also will develop new immunologic tests and strategies to help better determine how the results of animal studies should guide decisions about which pox virus candidates are most promising to move forward into human clinical trials.

The ultimate goal of the consortium is to advance the most promising new poxvirus vaccine candidate into Phase I clinical trials by the end of the grant period.

“Will our vectors work? I can't guarantee that,” Jacobs says. “But we will get a very quick idea of whether or not they will work better than anything we have tried before. We want to go all the way and get something into a clinical trial – and so, clearly, if we don't have at least one vector into clinical trials by the end of the five years, we will have failed.”