HIV vaccine trials are now under way

The latest U.S. estimates show that some 1 million to 1.2 million people in the United States are living with HIV/AIDS, with 24-27% undiagnosed and unaware of their HIV infection.1 What will it take to stem the spread of HIV in this country?

A new human clinical trial is under way at several sites around the country testing components of an experimental HIV/AIDS vaccine developed by researchers at the Yerkes National Primate Research Center of Emory University, GeoVax, and the Emory Vaccine Center, all in Atlanta, along with colleagues at the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). The vaccine technology is licensed to GeoVax, a biotechnology company aimed at development of human vaccines for diseases caused by HIV-1 and other infectious agents.

There are several studies in the field, in the United States and abroad, to test vaccine candidates, says Sarah Alexander, associate director of communications and external relations for the HIV Vaccine Trials Network (HVTN), an international collaboration of scientists and educators based in Seattle. The GeoVax trial is but one of at least 14 investigations tracked by HVTN to find an effective vaccine against the virus.

Review study design

A prototype of the GeoVax vaccine has been shown to be successful in containing a challenge virus and preventing progression to AIDS in 22 of 23 vaccinated rhesus macaque monkeys.2,3 A Phase I human safety trial was initiated in early 2003 and satisfactorily concluded in mid-late 2004.4

The vaccine includes two inoculations of a DNA vaccine that primes the immune system to recognize HIV and two doses of subsequent booster vaccine based on a recombinant modified vaccinia virus ankara (MVA) poxvirus.

The GeoVax vaccine produces the three major proteins expressed by HIV and is expected to induce the immune system to respond to these distinguishing features of HIV should the actual virus appear. Neither component of the vaccine incorporates the complete intact HIV virus.

The trials are comprised of two phases. The first phase is designed as a dose escalation to evaluate safety and immune responses. During this phase, scientists will administer low doses of the two vaccine components to a small number of volunteers. If the vaccine proves safe, it then will be tested at a high dose in a larger volunteer group. If success is achieved in the dose escalation studies, a second phase of clinical testing will be initiated.

The low dose group is fully enrolled, reports Harriet Robinson, PhD, professor and chief of microbiology and immunology at Emory University. The high-dose group was anticipated to begin enrollment in August 2006. "We should know the results from these groups in the fall of 2007," she says. "If the immunizations are safe and show elicited immune responses, we will then move to the evaluation of the immunization schedule."

The trials will include HIV-negative volunteers at several U.S. sites in the HIV Vaccine Trials Network, including the University of Alabama at Birmingham, Saint Louis (MO) University, the University of Maryland in College Park, and Vanderbilt University in Nashville, TN.

Understand the science

The GeoVax vaccine, as is many other HIV vaccines under development, is given in a prime/boost format. Why is this approach necessary?

According to information provided by the Pipeline Project, a collaboration between HVTN and the University of California San Francisco Center for HIV Information, the immune response from a single dose of an inactivated vaccine usually is not capable of providing effective protection. By repeating administration (boosting), scientists can enhance the immune response to a vaccine antigen.

The prime-boost approach calls for the administration of the same antigen in two vectors. Exposure to the antigen in the first vector primes the immune response, while re-exposure to the same antigen in the second vector boosts the response.

The GeoVax vaccine is but one of several candidates in the DNA plasmid class of HIV vaccines. Plasmids are small, circular piece of DNA found outside the chromosome in bacteria. Scientists are using plasmids as tools for inserting new genetic information into microorganisms.

References

1. Glynn M, Rhodes P. Estimated HIV prevalence in the United States at the end of 2003. Presented at the 2005 National HIV Prevention Conference. Atlanta; June 2005. Abstract 595.

2. Amara RR, Villinger F, Altman JD, et al. Control of a mucosal challenge and prevention of AIDS in rhesus macaques by multiprotein DNA/MVA vaccine. Science 2001; 292:69-74.

3. Robinson HL, Montefiori DC, Johnson RP, et al. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nat Med 1999; 5:526-534.

4. Korschun H. New clinical trial begins for HIV/AIDS vaccine developed at Emory and GeoVax. Press release; April 14, 2006. Accessed at: www.whsc.emory.edu/press_releases2.cfm?announcement_id_seq=6321.