www.hivandhepatitis.com

CMV Vaccine Clears SIV in Monkeys

Macaques given a CMV vector vaccine showed sustained CD8 T-cell activation, which was associated with control of a virus related to HIV.

As reported in the May 11, 2011, advance online edition of Nature, investigators tested a vaccine designed to protect against simian immunodeficiency virus (SIV), a relative of HIV that infects non-human primates.

The vaccine, consisting of SIV antigens combined with a cytomegalovirus (CMV) vector, stimulated an ongoing memory T-cell immune response, which appeared to inhibit mucosal SIV infection at the earliest stages. Nearly half of the macaques that received the CMV vaccine either alone or followed by an adenovirus vector vaccine demonstrated "early complete control" of SIV; 12 of these 13 monkeys showed protection lasting at least 1 year.

Below is an edited excerpt from a press release issued by Oregon Health and Science University explaining the research and its findings.

Non-Human Primate Studies Reveal
Promising Vaccine Approach for HIV

Hillsboro, OR -- May 11, 2011 -- Research conducted at Oregon Health and 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 Immunodeficiency Virus (HIV). Details of this advance are published in the advance online edition of the journal Nature. The paper will also be published in an upcoming print addition of the journal.

The research team, led by Louis Picker, MD, associate director of the OHSU VGTI and director of the VGTI's vaccine program, produced a vaccine candidate that programs the immune system of non-human primates to respond more swiftly to the presence of a primate version of HIV than it normally would. The team also included researchers from the National Cancer Institute-Frederick and the International AIDS Vaccine Initiative.

The VGTI researchers tested their vaccine candidate in rhesus macaque monkeys at the Oregon National Primate Research Center using a monkey form of HIV called Simian Immunodeficiency Virus (SIV). Of the monkeys that received the vaccine candidate, just more than half controlled replication of the virus to the extent that even the most sensitive tests could not detect signs of SIV.

To date, the vast majority of these animals have maintained control over the virus for more than a year, gradually losing any signs that they had ever been infected. In contrast, the macaques in the unvaccinated control group developed the monkey form of AIDS.

The researchers say that their work suggests that the immune responses elicited by this new vaccine candidate might completely clear SIV from animals that were initially infected. In comparison, antiretroviral therapy is able to control the disease, but cannot clear the virus from its hiding place within the immune systems own cells.

The VGTI team has been working for over ten years on its vaccine candidate, which is unique in using cytomegalovirus (CMV) as the transport system used to introduce the vaccine into the body. CMV was chosen because it is believed that most people are already infected with CMV, but for the majority, the virus causes little or no symptoms. In addition, once a person is infected with CMV, this virus remains in the body for life. Picker and his team hypothesized that if such a persistent virus were used as a vector it could create and maintain resistance against HIV by programming a portion of the body's immune system called effector memory T-cells to be constantly on the alert for the virus.

"The next step in vaccine development is to test the vaccine candidate in clinical trials in humans. For a human vaccine the CMV vector would be weakened sufficiently so that it does not cause illness, but will still protect against HIV," said Dr. Picker.

Investigator affiliations: Vaccine and Gene Therapy Institute, Departments of Molecular Microbiology and Immunology and Pathology, and the Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR; AIDS and Cancer Virus Program, SAIC Frederick Inc., National Cancer Institute-Frederick, Frederick, MD; International AIDS Vaccine Initiative, Vaccine Design and Development Laboratory, Brooklyn, NY. The National Institutes of Health and, the International AIDS Vaccine Initiative provided funding for this research.

5/17/11

Reference
SG Hansen, JC Ford, MS Lewis, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature (abstract). May 11, 2011 (Epub ahead of print).

Other Source
Oregon Health & Science University. Non-Human Primate Studies Reveal Promising Vaccine Approach for HIV. Press release. May 11, 2011.