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The Variable Vaccine for HIV

October 11, 2012

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Dr. Bertram Jacobs seeks to develop an elusive HIV vaccine. Jacobs spent this past summer as a Fulbright Specialist, providing HIV education to the Republic of South Africa.

Over 33 million people worldwide are infected with human immunodeficiency virus (HIV), and the race for a cure has, it seems, turned into a marathon. Though the road has been long, Bertram Jacobs, a virologist at Arizona State University, has achieved promising results in his efforts to develop an HIV vaccine. While Jacobs doesn’t deal in cures, his work has two main goals: the creation of a vaccine that can prevent infection or extend the life of HIV patients, and successful implementation of an educational curriculum for at-risk individuals that promotes safer sexual practices.

Jacobs moved to Phoenix 26 years ago, attracted by ASU’s potential for groundbreaking research. Nowa part of the Biodesign Institute at ASU, Jacobs touts the establishment for its research facilities and collaborative atmosphere, whichhas been vital to ASU’s prominent role in the development of vaccine technology.

“That is what’s special about Biodesign and School of Life Sciences,” Jacobs explains. “My lab uses pox viruses, Roy Curtiss’ lab uses salmonella, Charles Arntzen’s lab is using plants for vaccine vectors, and Jorge Reyes del Valle’s lab uses the measles virus as a vector. Here at ASU, we have the potential for using all of these different systems to find out what vector works best for any individual virus.” Recent findings from Jacobs’ collaborations hold promise for a variable approach to vaccines for HIV and other viruses.

In the current vaccination method, both initial immunization and booster doses of a vaccine are delivered the same way, usually by injecting less virulent (attenuated) virus proteins, inactivated virus proteins, or the virus’ genetic material intoa subject. All three generally elicit a mediocre immune response. 

An alternative method, which has been productive for Jacobs, is called heterologous prime boost vaccinations. The approach is two- pronged. An initial immunization is delivered in a genetically engineered Vaccinia pox virus, which then produces HIV proteins within the body. The use of live viral material improves the immune response over that attained from inactivated viral material. The second prong is a booster which contains proteins purified from mammalian cells engineered to produce HIV proteins. Such a dual delivery system improves immunogenicity – the ability for the vaccination to elicit an immune response and to stimulate specific immunity within an organism.

Over the last seven years, Jacobs and his collaborators, including those at the University of Lausanne in Switzerland, have worked to employ heterologous prime boost methodology in the design of a live, attenuated-vector HIV vaccine. Called NYVAC-C-KC, this vaccine provides an immunization of four HIV genes within the viral vector Vaccinia, followed by a boost with purified HIV proteins. Vaccinia, the largest mammalian virus, was used to make the first vaccine over 200 years ago, enabling the eradication of smallpox. The size of the virus facilitates the insertion of genetic material from other viruses such as HIV, and may prove invaluable for the cost-effectiveness of vaccines for countries that are struggling financially. “Rather than trying to develop two vaccines, for example, for two strains of HIV,” Jacobs explains, “we can make a single vaccine that can protect against both. For the developing world, this potential for multivalent vaccines is a truly remarkable implication.”

Though vaccines hold tremendous promise, they are not the final step in the fight against HIV. “A vaccine that earns a role in the war against HIV may only have 70 percent efficacy,” Jacobs warns. Thus, even if a successful vaccine is created, behavioral change is still the most important preventive measure against infection. For the last eight years, members of Jacobs’ lab have taken part in HIV prevention campaigns with Support for International Change. This organization is devoted to preventing the spread of HIV and acquired immune deficiency syndrome (AIDS) in underserved areas of Tanzania and providing humanitarian opportunities for undergraduate students across the globe. Jacobs teaches student volunteers about the psychology of behavioral change, as well as enough HIV biology to help promote safer sexual practices.

Ironically, a successful vaccine may make people less likely to alter their behavior. “It’s certainly possible that the impetus for behavioral change will go down if we get a vaccine,” Jacobs agrees. Preliminary trials suggest instead that the vaccine may work in concert with proper counseling and education. “Data from previous trials where subjects go in for a vaccine (or placebo) and receive counseling show that the number of sex partners patients have decreases and the amount of sex they have per week goes down. This is evidence that the counseling that goes on during the trials has a positive effect,” Jacobs said.

The success of the programs in Tanzania inspired Damien Salamone, a recent graduate from Jacobs’ lab, to establish another education program in Tanzania called HEAL (Health. Empowerment. Aid. Light.) International. While established programs focused on HIV and AIDS education, there was a lack of health services for people living with the virus. Educational programs focusing on other health issues were also largely unavailable until Salamone started HEAL International in 2005 to fill this void. His organization provides general health education focusing on HIV, AIDS, malaria, sanitation, nutrition and hygiene. The group also funds emergency medical support and provides financial aid for local women to start businesses that offer health services. Such health programs support the idea that education is imperative as a more immediate response to viruses than vaccine development, which often takes years of research and testing before a vaccine is released for public use.

Funding for vaccines is surprisingly problematic, especially when trying to market live, attenuated virus vaccines. “Our vaccines will not be as safe as non-replicating vaccines, but we really need a cost-benefit analysis. If one person dies from attenuated Vaccinia and you save 100,000 lives, from a public health point of view it is still worth the risk. For a pharmaceutical company, it’s not worth the investment, because they will be sued. We need to think on a societal level, rather than just an individual level,” Jacobs believes. Fortunately for Jacobs, the Bill and Melinda Gates Foundation invests in such societal thinking, and the foundation has granted Jacobs and his colleagues a three-year, $600,000 supplementary grant to pursue clinical trials.

With the success of NYVAC-C-KC non-human primate trials early in 2011 and human trials set to begin in 2012, a key mile-marker in the marathon fight against HIV may be fast approaching. Jacobs revels in this fact, believing now, more than ever, that he has the “best job in the world.” Sitting in his office, where he peers out at his colleagues over a desk covered with mountains of scattered articles, Jacobs’ devotion to gaining ground against HIV has eclipsed his concerns for his own future. Leaning back in his chair, tucked into his paper fortress, he grins and says, “I hope I put myself out of a job.”

Editor’s Note:

Selected for a Fulbright Specialist project in the Republic of South Africa, Bert Jacobs spent time this summer lecturing on the prospects for an HIV vaccine and on HIV prevention education. Jacobs is one of over 400 U.S. faculty and professionals traveling abroad this year through the Fulbright Specialists Program. Created in 2000 to complement the traditional Fulbright Scholar Program, the Specialists program provides short-term academic opportunities of two to six weeks to prominent U.S. faculty to support curricular and faculty development at post secondary, academic institutions around the world.

By Karla Moeller
Published in the summer issue of SOLS magazine
http://sols.asu.edu/publications/mag_vol8_01.php

 

Media contact:

Joe Caspermeyer
Biodesign Institute
Managing Editor
480-727-0369
joseph.caspermeyer@asu.edu
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