Curing Aids

 

 

Quick read

We've made major discoveries towards a cure for AIDS. Three HIV vaccines nearing clinical trials.

 

 

Scientists are finding the cure to stop a virus that has killed more than 25 million people. Research at the Lab targeting the immune response to HIV and viral mutation might stop the pathogen that causes AIDS.

Although current Human Immunodeficiency Virus (HIV) treatment hinders the infection rate and delays death, there is no HIV vaccine or cure available for the Acquired Immune Deficiency Syndrome (AIDS). The United Nations estimates 14 million children have been orphaned by this disease, and 40,000 Americans will likely become infected this year.

LANL researcher Bette Korber and her team are solving challenging problems regarding HIV evolution and transmission and, importantly, how the human immune system reacts to the virus. Korber's team is designing three vaccines to target this rapidly mutating virus. Animal tests are underway, with promising results and human trials will begin soon. These vaccines might finally deal a lethal blow to the AIDS virus.

"HIV expands and contracts like an accordion," Korber, recipient of acclaimed awards, told an audience during a Los Alamos lecture. "The mystery is why we can't clear it with our immune response."

The HIV virus's mechanisms make it extraordinarily good at avoiding triggering an immune response, making it nearly impossible to fight the infection. Korber's team's vaccine model is based on a mixture of synthetic proteins that address the virus's evasive nature. Not only does the HIV-1 virus mutate quickly, increasing its drug resistance, but its evolution affects the virus's sequence. The virus is also protected by a cloak of sugar molecules that prevents antibodies from blocking the HIV proteins used to invade the cell.

In mid-October, nine hundred experts convened at the international AIDS vaccine conference in South Africa. Doubts were expressed about whether a vaccine is on the horizon. "Fundamentally we don't understand enough about the human immune system and we don't know how the immune system deals with HIV," said Lynn Morris, conference co-chair.

Korber's HIV immunity research might quickly turn the tides.

Coming Together for a Common Goal

LANL knowledge of the virus's evolution and its diversity-aided by the Lab-designed GenBank, a database of all publicly available genetic sequences of nearly all organisms and the first pathogenic database-is impressive.

Los Alamos scientists work in a unique interdisciplinary environment that creates groundbreaking research. Scientists skilled in computation, modeling, and statistics used the Lab's world-class supercomputing facility to create optimized data that aligned HIV sequences, revealing that the virus's evolution began spreading through the human population as far back as 1930. Further modeling ruled out controversial theories about HIV's origin.

The Lab's Theoretical Biology and Biophysics Group played an integral part in clarifying the host-viral dynamics and the HIV evolution. Additional research, including use of an algorithm, unveiled how the human immune response affected viral variation. Also, Korber's team is defining human genes that increase HIV susceptibility.

This team also designed artificial HIV sequences that are highly similar to current strains; proteins from these sequences are now widely used to study cellular immune responses. Healthcare officials hope these proteins could lead to highly effective vaccines that combat AIDS.

Korber's team made a significant discovery about this dynamic virus. Detailed experiments revealed that the T cells (white blood cells) responsible for hosting HIV and allowing it to replicate remain alive only one day after production has begun, a vicious cycle. Her team determined HIV mutates quickly enough to be resistant to a single drug. This finding, along with observations that drug therapy could rapidly decrease the viral load, led to combination drug treatment for AIDS.

Korber and colleagues were able to demonstrate through theoretical and experimental approaches that virus survival is contingent upon viral lineage in addition to mutation, contrary to previous analysis methods and beliefs.

Additional AIDS Research

A Los Alamos National Laboratory mathematical model provided answers for the first time about offspring from a virus closely related to that which causes AIDS.

Thanks to this model, LANL researcher Alan Perelson and colleagues found that a single Simian Immunodeficiency Virus (SIV) produces about 50,000 offspring (viral burst) from a single cell, far more than previously believed. SIV and HIV infect hosts in highly similar ways.

With this information about SIV, AIDS researchers can more effectively create methods to reduce the number of virus progeny and limit infection.

Together, LANL AIDS researchers may soon find the answer to destroy this plague that is possibly the most dangerous disease the world has witnessed.