U of M study paves way for promising HIV vaccine
A study led by a University of Manitoba researcher has brought science one step closer to using the chickenpox virus to develop a vaccine against HIV.
“Varicella-zoster virus, which causes chickenpox, may hold the key to inducing the human body to produce a safe, long-lasting, protective immune response to HIV,” said Dr. Kelly MacDonald, professor of internal medicine, immunology and medical microbiology at the Max Rady College of Medicine in the Rady Faculty of Health Sciences and professor of immunology at the University of Toronto.
“Our study investigated an important safety concern that posed a barrier to this vaccine strategy. Now, with our findings, the stage is set to move forward with testing a chickenpox-based HIV vaccine.”
The study is the first in the world to demonstrate that chickenpox vaccine, when given to people who are already immune to it, does not trigger an unwanted “HIV-welcoming” immune state in the genital mucosa (lining) or in the bloodstream.
The study, Live-attenuated varicella-zoster virus vaccine does not induce HIV target cell activation, will be published in the Journal of Clinical Investigation and is now available online.
The project included researchers from the University of Toronto and the Kenyan AIDS Vaccine Initiative – Institute of Clinical Research at the University of Nairobi (Kenya). The U of M and the University of Nairobi have a long history of collaboration, dating back to 1980.
The study was supported by the Canadian Institutes of Health Research. Its lead author is Dr. Catia Perciani, a University of Toronto graduate student supervised by MacDonald.
MacDonald, head of the infectious diseases section in the U of M department of internal medicine, has worked in the field of host immunity to HIV and its application in vaccine design for more than 25 years. She sees potential in using the chickenpox virus in its vaccine form as a “vector” (carrier) to safely deliver HIV genes and generate immunity to HIV.
“A blended chickenpox/HIV vaccine would take advantage of the fact that chickenpox virus undergoes silent cycles of reactivation in the body. Each time it ‘wakes up’ from its dormant state, the body’s immunity quickly controls it, and the immunity is boosted,” MacDonald said.
“The idea is to combine what we call ‘HIV inserts’ with the chickenpox virus. We expect that each time the chickenpox virus is reactivated, it will also refresh immunity to HIV.”
Despite the promise of the vectored vaccine idea, MacDonald said, an international human clinical trial that used a different virus (adenovirus 5, or Ad5) as the vector for HIV genes was unsuccessful and had to be halted in 2007.
That vaccine had the unintended effect in people who were already immune to Ad5 of activating HIV “target cells” in mucosal surfaces, including the genital area. This may have increased their susceptibility to HIV infection.
The purpose of MacDonald’s study was to investigate whether chickenpox virus posed the same risk of this unwanted effect.
Her study was conducted in Kenya, a country severely affected by the HIV epidemic. The research participants were 44 healthy, HIV-negative women who were at low risk for HIV exposure and tested positive for immunity to chickenpox.
Researchers injected the women with a high-dose vaccine against only chickenpox virus. They tested each participant’s blood, as well as mucosal cells from her cervix and rectum, at intervals of four, eight and 12 weeks.
The key finding was that 12 weeks post-vaccination, there was no significant difference in the frequency of activated HIV target cells, compared to pre-vaccination.
The study also showed that the vaccine vigorously boosted the women’s existing immunity to chickenpox, not only in their bloodstream but in their genital area. This immune response in the genital area, where HIV infection first occurs, is a highly positive finding for the HIV vaccine concept.
“This chickenpox vaccine passed this comprehensive safety examination,” MacDonald said. “Our results pave the way for the use of chickenpox virus as a vector for HIV vaccine development.”
The next steps, the scientist said, are to continue testing the vaccine strategy using non-human primates and to start developing a chickenpox virus-vectored HIV vaccine for a clinical trial in humans.