New research helps explain why AIDS vaccine has been so difficult to develop

September 9, 2012

For decades, a successful HIV vaccine has been the Holy Grail for researchers around the globe. Yet despite years of research and millions of dollars of investment, that goal has still yet to be achieved. Recent research by Oregon Health & Science University scientists explains a decades-old mystery as to why slightly weakened versions of the monkey AIDS virus were able to prevent subsequent infection with the fully virulent strain, but were too risky for human use, and why severely compromised or completely inactivated versions of the virus were not effective at all.

The research was conducted at OHSU's and Gene Therapy Institute and is published online in the journal Nature Medicine.

Traditionally, there have been two methods for creating vaccines to combat infectious disease. The first approach utilizes a live, yet weakened strain of the disease in question. This weakened strain is not strong enough to cause illness yet potent enough to activate the immune system so that it can detect and fight a disease if it enters the body in the future. The second approach makes use of a dead form of the disease. As with the other approach, the introduction of the disease in a safe form educates and prepares the body for a possible future invasion.

In the early 1990s, a slightly weakened version of SIV, the monkey counterpart to HIV, was shown to protect monkeys for infection with the fully virulent version, but this weakened version was still able to cause AIDS in some monkeys and the protection was lost if the vaccine was further weakened.

"Efforts to develop a live attenuated virus are analogous to the tale of 'Goldilocks and the Three Bears,'" explained Louis Picker, M.D., associate director of the OHSU Vaccine and Gene Therapy Institute. "The field was looking for a vaccine that was 'not too hot,' or 'not too cold,' but 'just right.' The problem was that it appears that weakening a virus to the level that is 'just right' is impossible. However, we thought that understanding the mechanism responsible for the protection afforded by the too-dangerous-for clinical-use attenuated vaccine would allow us to design a vaccine that would be both effective and safe".

The newly published research shows that the protection is due to anti-viral T cells maintained in lymphoid tissue by persistent live attenuated virus; weakening the virus prevents this persistence and curtails protection. Thus, unlike most vaccines, an effective might have to persist in the body to be effective.

Picker's group has developed another persistent virus named cytomegalovirus (CMV) engineered to express SIV or HIV proteins and serve as the transport system (vector) used to raise protective immune responses against these AIDS-causing viruses. In May 2011, the Picker lab published findings that demonstrated how immune responses elicited by their vaccine candidate were able to completely control SIV in a significant number of exposed animals.

CMV is a persistent virus that most people carry, causes few or no symptoms, and elicits very strong cellular responses that are maintained for life. These immune responses are characterized by a type of T cell called an effector memory T cell that has potent anti-viral function and localizes in the same tissues targeted by the -causing viruses. Picker and his team hypothesize that CMV vector-generated anti-HIV responses would be constantly on the alert for HIV and would be able to intercept and stop infection immediately after exposure.

Explore further: Non-human primate studies reveal promising vaccine approach for HIV

Related Stories

Non-human primate studies reveal promising vaccine approach for HIV

May 11, 2011
(PhysOrg.com) -- Research conducted at Oregon Health & Science University's Vaccine and Gene Therapy Institute (VGTI) has developed a vaccine candidate in non-human primates that may eventually lead to a vaccine against Human ...

Antibodies help protect monkeys from HIV-like virus, scientists show

May 5, 2011
Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). ...

Recommended for you

Study suggests a way to stop HIV in its tracks

December 1, 2017
When HIV-1 infects an immune cell, the virus travels to the nucleus so quickly there's not enough time to set off the cell's alarm system.

Discovery puts the brakes on HIV's ability to infect

November 30, 2017
Viewed with a microscope, the virus faintly resembles a pineapple—the universal symbol of welcome. But HIV, the virus that causes AIDS, is anything but that. It has claimed the lives of more than 35 million people so far.

Rising levels of HIV drug resistance

November 30, 2017
HIV drug resistance is approaching and exceeding 10% in people living with HIV who are about to initiate or reinitiate first-line antiretroviral therapy, according to the largest meta-analysis to date on HIV drug resistance, ...

Male circumcision and antiviral drugs appear to sharply reduce HIV infection rate

November 29, 2017
A steep drop in the local incidence of new HIV infections accompanied the rollout of a U.S.-funded anti-HIV program in a large East-African population, according to a study led by researchers at Johns Hopkins Bloomberg School ...

Combination HIV prevention reduces new infections by 42 percent in Ugandan district

November 29, 2017
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections ...

Research on HIV viral load urges updates to WHO therapy guidelines

November 24, 2017
A large cohort study in South Africa has revealed that that low-level viraemia (LLV) in HIV-positive patients who are receiving antiretroviral treatment (ART) is an important risk factor for treatment failure.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.