Strategy to Help Vaccines Outsmart HIV

A new discovery at Oregon Health & Science University highlights an ingenious method to ensure the body effectively reacts when infected with the highly evasive HIV virus that causes AIDS. 

The same team of researchers has been utilizing this unique approach to develop its own HIV vaccine candidate, which has so far shown promising results in animal studies.

A major challenge in developing an effective HIV vaccine is figuring out how to target this evasive virus," said Dr. Louis Picker, M.D., associate director of the OHSU Vaccine and Gene Therapy Institute, where the work was conducted.

CD8+ "cytotoxic" T cells are an important component of the immune system and are particularly important for pathogens, like HIV, that easily evade antibodies. They serve as sentries within the body that detect and destroy virus-infected cells, accomplishing this function by recognizing short viral peptides on the surface of infected cells. T-cells are designed to be quite frugal in the number of different viral peptides they recognize, typically responding to just a handful of such peptides. This is a problem for control of HIV, which is able to able change its peptides and thus escape T cells responses that do not target the relatively few functionally critical peptides that can't change without debilitating the virus. In the vast majority of HIV infections, the few viral peptides recognized by T cells are not the vulnerable ones, and the virus escapes.

Therefore, the strategy that Dr. Picker and his colleagues adopted was to try to develop a vaccine to increase the number of viral peptides that T cells would recognize, reasoning that increasing this "recognition breadth" would allow T cells to more effectively respond to HIV.

The researchers found that cytomegalovirus or CMV, a common virus already carried by a large percentage of the population, may hold the key. Their studies in the non-human primate model of HIV, called SIV, found that a modified version of CMV engineered to express SIV proteins generates SIV-specific T cells that recognize three-fold as many SIV peptides as T cell generated by conventional vaccines and SIV itself. 

Moreover, these responses were entirely different from conventional responses, such that even viruses that had previously escaped natural responses would still be vulnerable. In effect, the hunters of the body were provided with a much better targeting system to help them find and destroy an elusive enemy.

Picker and his colleagues believe an HIV vaccine equipped with a modified CMV vector might be able to both prevent infection (prophylactic vaccine) and effectively battle the virus even if applied post-infection in individuals with infections suppressed by anti-retroviral therapy. Moving forward, the research team hopes to utilize this new information to create customized CMV vectors with a broad ability to identify several components of HIV and then incorporate this component into an effective vaccine.

"We hope we can begin clinical trials in human patients within a few years," explained Dr. Picker. "This new information gives us a much clearer roadmap for effectively targeting the disease which to this point has found ways to evade the human immune system."

HIV Drugs May Help Protect Young Patients' Hearts

Long-term use of powerful drug cocktails known as highly active antiretroviral therapy (HAART) may help protect the hearts of children and teens infected with HIV.

HAART is a form of antiretroviral therapy that is widely used to treat people with HIV, the virus that causes AIDS. Prior to the introduction of antiretroviral therapies, youngsters infected with HIV were at increased risk for heart failure. 

Since the advent of powerful HIV-suppressing medications, "the effects of HIV and on the cardiovascular system of HIV-infected children are not completely understood. 

The new study sought to clear that up. It included nearly 600 HIV-infected and uninfected patients from 14 pediatric HIV clinics across the United States.
According to the team, heart function was better among HIV-infected children receiving HAART than those who were infected with HIV and did not receive HAART, and children who were exposed to HIV but not infected.
"Our results indicate that the current use of combination [antiretroviral therapy], usually HAART, appears to be cardioprotective in HIV-infected children and adolescents," the study authors reported. "This finding is even more relevant in the developing world where the prevalence of HIV disease in children is much higher."
The researchers added that further study comparing different drug regimens might be beneficial "in optimizing HIV outcomes and protecting long-term cardiac health" of children with HIV.

New Tool for Identifying Powerful HIV Antibodies

A team of NIH scientists has developed a new tool to identify broadly neutralizing antibodies (bNAbs) capable of preventing infection by the majority of HIV strains found around the globe, an advance that could help speed HIV vaccine research. Scientists have long studied HIV-infected individuals whose blood shows powerful neutralization activity because understanding how HIV bNAbs develop and attack the virus can yield clues for HIV vaccine design.

But until now, available methods for analyzing blood samples did not easily yield specific information about the HIV bNAbs present or the parts of the virus they targeted. In addition, determining where and how HIV bNAbs bind to the virus has been a laborious process involving several complicated techniques and relatively large quantities of blood from individual donors.

The new tool lets scientists determine precisely the HIV bNAbs present in a particular blood sample by analyzing the neutralized HIV strains there.
Calledneutralization fingerprinting, the tool is a mathematical algorithm (a problem-solving procedure) that exploits the large body of data on HIV bNAbs generated in recent years. The neutralization fingerprint of an HIV antibody is a measurement of which virus strains it can block and with what intensity.
Antibodies that target the same portion of the virus tend to have similar fingerprints.

Blood samples contain mixtures of antibodies, so the new algorithm calculates the specific types of HIV bNAbs present and the proportion of each by comparing the blood's neutralization data with the fingerprints of known HIV bNAbs. This approach is particularly useful when other methods of determining bNAbs targets in a blood sample are not feasible, such as when just a small amount of blood is available. Neutralization fingerprinting also is significantly faster than older analytic methods.

According to the researchers who developed the assay, the underlying approach could be applied to the study of human responses to other pathogens, such as influenza and hepatitis C viruses, for which scientists have much information about neutralizing antibodies.

Human Breast Milk Can Help Reverse Antibiotic Resistance.

A protein complex found in human breast milk can help reverse the antibiotic resistance of bacterial species that cause dangerous pneumonia and staph infections, according to new University at Buffalo research.

In petri dish and animal experiments, the protein complex -- called Human Alpha-lactalbumin Made Lethal to Tumor Cells (HAMLET) -- increased bacteria's sensitivity to multiple classes of antibiotics, such as penicillin and erythromycin.

The effect was so pronounced that bacteria including penicillin-resistantStreptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) regained sensitivity to the antibiotics they were previously able to beat.