New Research Points to New Route for Developing HIV Vaccine

By tracking the earliest days of one person’s robust immune response to HIV, researchers at Duke and the NIH Vaccine Research Center have begun to chart a new route for developing a vaccine that may boost the body’s ability to neutralize the virus.
The research team, led by Barton F. Haynes, MD, director of the Duke Human Vaccine Institute, and John Mascola, MD, acting director of the NIH Vaccine Research Center, have for the first time described the co-evolution of antibodies and virus in a person with HIV whose immune system mounted a broad attack against the pathogen. Their findings were published April 3, 2013, in the journal Nature.
Most vaccines work by inducing this antibody response, but the HIV virus has proved to be a difficult vaccine target. When HIV antibodies are produced, they typically have a limited range, and the virus changes rapidly to escape harm.
The current research was aided by new technologies that can detect early infection and track the subsequent immune response and virus evolution.
“This project could only have been carried out by a multidisciplinary team working closely together,” said Dr. Haynes, who led the work as a project of the Duke Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) consortium, which is funded by the National Institute of Allergy and Infectious Diseases. “For the first time, we have mapped not only the evolutionary pathway of the antibody, but also the evolutionary pathway of the virus, defining the sequence of events involved that induce the broadly neutralizing antibodies.”
The key to this finding was a person in Africa whose HIV infection was detected so early that the virus had not yet mutated to avoid the immune assault. This person also exhibited a trait that occurs in only about 20% of people infected with HIV – an immune system that produces broadly neutralizing antibodies. These immune weapons attack vulnerable sites of the virus that are conserved despite mutations. In identifying the early viral infection, the team found the outer envelope, the viral surface glycoprotein, which triggered the start of the broadly neutralizing antibody development.
By tracking the precise virus and antibody pathways involved, the Duke CHAVI-ID and NIH teams now have a detailed road map for development of a potential vaccine, which involves immunogens with an outer envelope specifically selected to stimulate the production of broadly neutralizing antibodies.
“The next step is to use that information to make sequential viral envelopes and test them as experimental vaccines,” Dr. Haynes said. “This is a process of discovery and we’ve come a long way with regard to understanding what the problem has been.”

Genetic Link Connecting Diabetes and Alzheimer's?

Researchers at the City College of New York have published the results of a study that indicates that a single gene forms a link between diabetes and Alzheimer’s disease.

Biology Professor Chris Li and her colleagues write that the gene, which is known to be present in many Alzheimer’s disease cases, affects the insulin pathway. That kind of disruption of the insulin pathway is a prominent feature of diabetes.

The story is published in the June 2012 issue of Genetics.

According to Professor Li, “People with Type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy.”

Professor Li and her colleagues hope that the new insights into the genetic link between the two diseases will help focus research in ways that might lead to new therapies in the treatment of both.

Study Links Premature Birth to Later Psychiatric Disorders

The King’s College London has reported that one of the largest studies to investigate birth complications and later mental health has found that premature birth constitutes a single, independent risk factor for a range of severe psychiatric disorders. Researchers at the Institute of Psychiatry (IoP) at King’s College London and Karolinska Institutet in Sweden suggest that neuro-developmental differences in those born prematurely may be important in understanding the link.

This study, which has been published in The Archives of General Psychiatry, found that persons born very prematurely, which is defined as less than 32 weeks gestation, were three times more likely to be hospitalized with a psychiatric disorder at age 16 years and older, compared to those born at term, which is defined as 37 to 41 weeks gestation. The risk varied depending on the condition -- for psychosis it was 2.5 more likely, for depression three times more likely, and for bipolar disorder 7.4 times more likely. The findings also revealed a smaller increased risk for those born moderately prematurely, which is defined as 32 to 36 weeks.

Previous research has shown an association between premature birth and an increased risk of schizophrenia, but this report claims that this is the first study to demonstrate an association with a broad range of psychiatric disorders, including bipolar disorder, psychosis, and depression.

Dr. Chiara Nosarti, lead author of the paper at the IoP at King’s, says, “We found a very strong link between premature birth and a range of psychiatric disorders. Since we considered only the most severe cases that resulted in hospitalization, it may be that in real terms this link is even stronger. However, it is important to remember that even with the increased risk, these disorders still only affect 1% to 6% of the population.”

The researchers analyzed data from nearly 1.5 million Swedish birth and medical records between 1973 and 1985 and identified all those admitted to hospital with their first episode of a psychiatric disorder by 2002.

Dr. Nosarti says, “We believe that the increased risk of mental disorders in those born very prematurely can be explained by subtle alterations of brain development. The immature nervous system in those born prematurely is particularly vulnerable to neonatal brain injury resulting from birth complications.”

Dr. Nosarti continues, “The strongest association we found in this study was to mental health disorders known to have a strong biological basis, such as bipolar disorder, further adding to the theory that neuro-developmental differences in those born prematurely may play an important role for later mental health.’”

The authors point to the importance of raising awareness of the increased risk of mental health disorders in people born prematurely and suggest gestational age should be considered when investigating psychiatric disorders in young adults.

Dr. Nosarti concludes, “Future investigations of the mechanisms associated with the increased risk of mental health following preterm birth may aid the early identification of high-risk children, who could then be prospectively identified and closely monitored – to decide if, when, and what interventions may be appropriate.”

This study was funded by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Brain and Behavior Research Foundation and supported by the National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King’s College London.

Brown University Study Reports Higher Education Lowers Blood Pressure

In a paper published online recently in the open access journal BMC Public Health, a Brown University assistant professor says that he and his co-authors may be able to help explain the previously documented correlation in developing countries between education and a lower risk of heart disease.

Eric Loucks, an assistant professor of community health at Brown, addressed the question of whether education influences heart disease. “One of the ways to get at that is to see if education is related to the biological underpinnings of heart disease, and one of those is blood pressure.”

In the paper, Loucks and his co-authors analyzed almost 4,000 records from the Framingham Offspring Study.

Controlling just for age, the study’s authors found that women who completed 17 years of school or more had systolic blood pressure readings that were, on average, 3.26 millimeters of mercury (mmHg) lower than women who did not finish high school. Women who went to college, but did not pursue graduate studies, had a 2 mmHg benefit compared to less educated women. For men, going to graduate school versus not finishing high school made a 2.26 mmHg difference, with a lesser benefit for going to college.

Even after controlling for influences such as smoking, drinking, obesity and blood pressure medication, the benefit persisted, although at a lower level (graduate school gave a benefit of 2.86 mmHg for women and 1.25 mmHg for men).

Professor Loucks then went even further in his analysis by indexing the blood pressure readings to make them all equal at the beginning of the 1971-2001 Framingham study period. This statistical maneuver enabled him to determine whether the analysis measured a static difference apparent early on in life or whether the differences increased at all over time. The most educated group of women retained a 2.53 mmHg benefit over the least educated. In men, the difference was much less, only 0.34 mmHg.

That the gender differences are so pronounced and appear to become more so as life goes on suggests that education may have a greater impact on women’s health over their lifetime than on men’s health, Professor Loucks said. That could be because of the correlation between low educational attainment and other health risk factors found in other studies of women.

“Women with less education are more likely to be experiencing depression, they are more likely to be single parents, more likely to be living in impoverished areas and more likely to be living below the poverty line,” Professor Loucks said.

One caveat, he said, is that the population in the study, drawn from the suburban community of Framingham, Massachusetts, decades ago, is disproportionately white and that the conclusions might not generalize to other races.