Two presentations on Emory research at last week’s AIDS Vaccine 2010 conference concerned adjuvants. These are substances that act as amplifiers, stimulating the immune system while keeping its focus on the specific components of a vaccine.
Charlie Janeway (1943-2003)
Immunologist Charlie Janeway once described adjuvants as immunology’s “dirty little secret,” because for a long time scientists did not know how they worked. Some adjuvants can sound irritating and nasty, such as alum and oil emulsion. Alum is the only vaccine adjuvant now licensed for human clinical use in the US. Over the last few years, scientists have learned that adjuvants rev up what is now known as the “innate immune system,” so that the body knows that the vaccine is something foreign and dangerous.
Rama Rao Amara, a vaccine researcher at Emory Vaccine Center and Yerkes National Primate Research Center, and Harriet Robinson, former head of microbiology and immunology at Yerkes and now chief scientific officer at the firm GeoVax, both described extra ingredients for the DNA/MVA vaccine that Robinson designed while at Yerkes in collaboration with NIH researchers.
Imagine that HIV was a “normal” virus. An infection begins and the body responds, without getting trapped in a cycle where CD4+ T cells are consumed and the immune system is crippled.
SIV can infect sooty mangabeys but it doesn't cripple their immune systems.
The attractiveness of this idea explains some of why scientists are interested in sooty mangabeys and other non-human primates. HIV’s relative SIV can infect them, but they usually don’t develop immunodeficiency.
At last week’s AIDS Vaccine 2010 conference, Cynthia Derdeyn reported her laboratory’s recent results investigating sooty mangabeys, which don’t develop high levels of neutralizing antibodies against SIV when infected. Derdeyn’s group at Emory Vaccine Center andÂ Yerkes National Primate Research Center studies how HIV and SIV evade the immune system.
How you vaccinate helps determine how you protect. This idea lies behind many researchers’ interest in mucosal vaccines. How a vaccine is administered (orally/nasally vs intramuscular, for example) could make a difference later, when the immune system faces the bad guys the vaccine is supposed to strengthen defenses against.
How does the route of immunization affect the quality of immunity later on? For example, is a nasal spray best when trying to prevent respiratory infections?
A recent paper from Emory Vaccine Center director Rafi Ahmed’s laboratory challenges this idea. The paper was published in the Journal of Immunology. Scott Mueller, now an Australian Research Council research fellowÂ at the University of Melbourne, is first author.
Memory T cells are a key part of a response to a vaccine, because they stick around after an infection, enabling the immune system to fight an invading virus more quickly and strongly the second time around. In the paper, the Emory team compared memory T cells that form in mice after they are infected in the respiratory system by a flu virus or throughout their bodies by a virus that causes meningitis (lymphocytic choriomeningitis virus or LCMV).
The authors engineered a flu virus to carry a tiny bit of LCMV (an epitope, in immunological terms) so that they could compare apples to apples by measuring the same kind of T cells. They found that memory T cells generated after a flu infection are weaker, in that they proliferate and stimulate other immune cells less, than after a LCMV infection. This goes against the idea that after a respiratory infection, the immune system will be better able to face a challenge in the respiratory system.
Bali Pulendran, PhD
A tiny invader, perhaps a virus or a microbe, enters the body, and our ancient immune system responds. But how does it know what kind of invader has landed? And once it knows, how does it decide what kind of immune response it should launch?
In humans, the immune system consists of two parallel systems working with one another to fend off invaders. One is the innate immune system, the other the adaptive immune system.
Immunologist Bali Pulendran studies how those two systems work together to identify and respond to all kinds of intruders including pathogens, viruses and microbes.
Itâ€™s the innate immune systemâ€™s job to recognize the first signs of infectionâ€”that is, the moment a pathogen enters the body. â€œIn a sense they act as smoke detectors if you will,â€ says Pulendran. â€œLittle alarms.â€
Riders gather at the Hope Clinic of the Emory Vaccine Center for the final leg of their ride.
More than 130 bicyclists rode 200 miles in two days to raise $188,660 for AIDS vaccine research at the Emory Vaccine Center. The AIDS Vaccine 200 on May 22-23, sponsored by Action Cycling Atlanta, was the eighth annual ride. The series now has raised more than $680,000 for AIDS vaccine research.
This year’s riders traveled from Emory to Eatonton, Georgia, and back to Emory along with a volunteer crew.
Because of generous sponsorships, Action Cycling donates 100 percent of funds raised by participants to AIDS vaccine research. These unrestricted funds fill gaps that cannot be met by grant dollars alone.
Posted on June 11, 2010
Paula Frew, PhD, MPH
Although African Americans make up a significant share of HIV cases in the U.S., they are underrepresented in HIV clinical trials. New research shows that promotion of HIV clinical trials and participation by African Americans can be increased by coalitions that link community organizations to clinical-research institutions.
â€œCommunity organizations already have built trusting relationships in their communities,â€ saysÂ Paula Frew, PhD, assistant professor of medicine at Emory School of Medicine. â€œIf HIV/AIDS prevention and HIV clinical research become part of the agendas of these organizations, they can become ideal allies for increasing participation by community members who are at risk for disease.â€
Frew was lead investigator in a study published recently in the Journal Prevention Science. SheÂ is director of health communications & applied research at the Hope Clinic of the Emory Vaccine Center and an investigator in the Emory Center for AIDS Research (CFAR).