Research on immune cells “exhausted” by chronic viral infection provides clues on how to refine cancer immunotherapy. The results were published Tuesday, Dec. 3 in Immunity.
Scientists at Emory Vaccine Center, led by Rafi Ahmed, PhD, have learned about exhausted CD8 T cells, based on studying mice with chronic viral infections. In the presence of persistent virus or cancer, CD8 T cells lose much of their ability to fight disease, and display inhibitory checkpoint proteins Read more
But then I realized that this might beÂ an example of “burying the lead,” since we haven’t made a big hoopla about the underlying vaccineÂ studies, conducted by Rama Amara. Some of these studiesÂ showed that a majority of monkeys can beÂ protected from repeated viral challenge.Â TheÂ more effective vaccine regimens include adjuvants such asÂ the immune-stimulating molecules GM-CSF or CD40LÂ (links are the papers on the protective effects). Read more
Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.
In recent years, researchers interested in a “universal flu vaccine” identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn’t mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.
In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.
The results were published Monday, August 25 inÂ PNAS.
The key to having volunteers’ bodies produce antibodies against the stem region seemed to be their immune systems’ unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.
Note: for a counterpoint, check out this 2013 Science Translational Medicine paper on how vaccination that induces anti-stem antibodies contributes toÂ enhanced respiratory disease in pigs.
Immunologists reported recently that the drug rapamycin, normally used to restrain the immune system after organ transplant, has the unexpected ability to broaden the activity of a flu vaccine.
The results, published in Nature Immunology, indicate that rapamycin steers immune cells away from producing antibodies that strongly target a particular flu strain, in favor of those that block a wide variety of strains. The results could help in the effort to develop a universal flu vaccine.
This study was inspired by a 2009 Naturestudy from Koichi Araki and Emory Vaccine Center director Rafi Ahmed, reports Jon Cohen in Science magazine. Read more
Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a â€œHuman Vaccines Projectâ€. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.
The idea behind a â€œHuman Vaccine Projectâ€ is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.
Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendranâ€™s laboratory on â€œsystems vaccinologyâ€ and their analysis of the yellow fever vaccine as an example.
One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.
An interesting related tidbit:
There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.
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.
â€œOnly occasionally are there scientific challenges that unite people powerfully towards a common goal,â€ Wagner said. â€œWe are proud for the role weâ€™ve been able to play in the pursuit of vaccine research. I am particularly pleased that so many students and young investigators have been able to participate in this conference.â€
John Mascola from the Vaccine Research Center at the NIH gave the dayâ€™s first scientific talk, describing the discovery of broadly cross-reactive neutralizing antibodies to HIV and the ability to isolate those antibodies. This is the kind of recent discoveries that has re-energized the HIV vaccine research community.
Bette Korber of the Los Alamos National Laboratory noted that HIV mutations that escape immune response in some infected people are frequently susceptible in others. New â€œmosaic vaccinesâ€ can expand the breadth and depth of these immune responses, she said. She also described the effort underway in her laboratory to re-examine results of an earlier vaccine trial, VAX004, in light of new analytic strategies.
Giuseppe Pantaleo of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland expressed the need to implement adaptive clinical trial study design. This theme â€” the need to examine clinical trial results early and often, and then adapt, rather than waiting for all results at the very end of a years-long trial â€” has been echoed often at the conference.
At a midday press briefing, Peter Kwong of the NIH Vaccine Research Center discussed his research with broadly neutralizing antibodies, one of which attacks the initial site of vital attachment to CD4 T cells.
Hendrik Streek from Harvardâ€™s Ragon Institute described how vaccines induce antibody and CD4 response and contraction. Even though CD4 cells are the ones attacked during HIV infection, Streek believes CD4 responses may be a missing link to effective vaccine development
Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, led a discussion of the new Enterprise Scientific Strategic Plan. Less than two out of five people who need treatment for HIV are receiving it, said Bernstein, which underscores the importance of an effective vaccine.
The new plan arrives at a time of great momentum and excitement in the field. A year of important advances has included discoveries about broadly neutralizing antibodies, new technologies, and a vaccine that demonstrated an immune response. The plan emphasizes novel clinical trials design, a strong commitment and engagement by many partners, and expanded diversity of funding by many stakeholders.
Jose Esparza, senior advisor on HIV vaccines to the Bill & Melinda Gates Foundation, emphasized the need to rapidly capitalize on new science, and said HIV vaccines are one of the foundationâ€™s top priorities. High risk, high reward projects will be funded through the Gates Grand Challenges Explorations grants.