At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy.
The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 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
Yerkes immunologist Guido Silvestri and colleagues have a paper in PLOS PathogensÂ shedding light on the still singular example of Timothy Brown, aka “the Berlin patient”, the only human cured of HIV. Hat tip to Jon Cohen of Science, who has a great explanatory article.
Recall that Brown had lived with HIV for several years, controlling it with antiretroviral drugs, before developing acute myeloid leukemia. In Berlin, as treatment for the leukemia, heÂ received aÂ bone marrow transplant — and not just from any donor; the donor had a HIV-resistance mutation. What was the critical ingredient that enabled HIV to beÂ purged from his body?
Conditioning: the chemotherapy/radiation treatment that eliminates the recipient’sÂ immune system before transplant? HIV-resistant donorÂ cells? Or graft-vs-host disease: the new immune system attacking theÂ old?
Silvestri and colleagues performed experiments with SHIV-infected non-human primates that duplicate most, but not all, of the elements of Brown’s odyssey. The results demonstrate that conditioning, by itself, does not eliminate the virus from the body. But in one animal, it came close.Â Frustratingly, that animal’s kidneys failed and researchers had to euthanize it. In two others, the virus came back after transplant.
A critical difference from Brown’s experience is thatÂ monkeys received their own virus-free blood-forming stem cells instead of virus-resistant cells. Cohen reports thatÂ Silvestri hopes to do future monkey experiments that test more of these variables, including transplanting the animals with viral-resistant blood cells that mimic the ones that Brown received.Â
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
Studying lampreys allows biologists to envision the evolutionary past, because they represent an early offshoot of the evolutionary tree, before sharks and fish. Despite their inconspicuous appearance, lampreys have a sophisticated immune system with three types of white blood cell that resemble our B and T cells, researchers have discovered.
Scientists at Emory University School of Medicine and the Max Planck Institute of Immunology and Epigenetics in Freiburg have identified a type of white blood cell in lampreys analogous to the “gamma delta T cells” found in mammals, birds and fish. Gamma delta T cells have specialized roles defending the integrity of the skin and intestines, among other functions.
The results are published in the journalÂ Nature. The finding follows anÂ earlier studyÂ showing that cells resembling two main types of white blood cells, B cells and T cells, are present in lampreys.
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.
Emory influenza researchers Richard Compans, Anice Lowen and John Steel are co-signers of a statement announcing the end of a self-imposed moratorium on H5N1 avian flu research.
Last year, an international group of researchers called for the moratorium after public concern over studies of H5N1 transmissibility in ferrets, a model for spread of infection between humans. The group of researchers has now recommended ending the moratorium, citing safeguards and safety review procedures put in place by the National Institutes of Health and authorities in other countries. From the letter published today in Science and Nature:
In January 2012, influenza virus researchers from around the world announced a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals. We declared a pause to this important research to provide time to explain the public-health benefits cheap oakley of this work, to describe the measures in place to minimize possible risks, and to enable organizations and governments around the world to review their policies (for example on biosafety, biosecurity, oversight, and communication) regarding these experiments.
…Thus, acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies.
Compans is professor of microbiology and immunology at Emory University School of Medicine and scientific director of Emory’s Influenza Pathogenesis and Immunology Research Center. Lowen and Steel are assistant professors of microbiology and immunology at Emory and IPIRC investigators.
Francis Collins, director of the National Institutes of Health, made a splash last week predicting the arrival of a universal flu vaccine in the next five years.
Francis Collins told USA Today he is "guardedly optimistic" about the possibility of long-term vaccination that could replace seasonal flu shots.
His prediction came at the same time as a report in Science identifying an antibody that can protect against several strains of the flu virus.Â Taking a look at the Science paper, how the scientists found the “super antibody” seems remarkably similar to how Emory’s Jens Wrammert, Rafi Ahmed and colleagues found a similar broadly protective antibody.Â Their results were published in the Journal of Experimental Medicine in January.
In both cases, the researchers started with someone who had been infected with the 2009 H1N1 swine origin flu virus, sifted through the antibodies that person produced and found some that reacted against several varieties of the flu virus. There must be something special about that 2009 pandemic strain!
The Pap smear â€“ also called Pap test â€“ is part of the standard annual wellness exam for womenâ€™s health and used as a first step in detecting cervical cancer.Â But according to a recent article published in the International Journal of Cancer,Â the Pap test may not provide reliable results for certain types of cancer that are harder to detect.
Kevin Ault, MD, associate professor of obstetrics and gynecology at Emory University School of Medicine and investigator at the Emory Vaccine Center conducted a post-hoc analysis of the FUTURE I and FUTURE II (Gardasil) vaccine trials.Â Based on that analysis Ault, a leading expert and pioneer in the field of human papilloma virus (HPV), says a regular Pap test is not always effective in diagnosing adenocarcinoma, because it starts high up in the cervical canal and may not be sampled by the Pap smear.
â€œThere are a number of reasons the Pap smear could lead to inaccurate results. For example, the pathologist examining the cells could make an error, the gynecologist may not sample the cervix adequately or an infection could obscure the results,â€ says Ault.
According to Ault, andenocarcinoma is the second most common type of cervical cancer, accounting for about 20 percent of all cervical cancer cases. While the overall incident of cervical cancer is on the decline, Ault reports the proportion of cervical cancers that are andenocarcinoma is rising.
Cervical cancer is the eighth most common type of cancer in American women. More than 12,000 new cases of invasive cervical cancer are diagnosed each year, and more than 4,200 women in the U.S. die from of this disease annually* according to the American Cancer Society.Â Scientists believe that pre-invasive cervical cancer may develop over a period of months or years after the cervix is infected with the sexually transmitted HPV.
â€œThe take-away from this recent paper is the HPV test would be a better test for the harder to detect adenocarcinoma cervical cancer, if not all cervical cancer,â€ says Ault.
Scientists at Emory and the University of Chicago have discovered that the 2009 H1N1 flu virus provides excellent antibody protection. This may be a milestone discovery in the search for a universal flu vaccine.
Researchers took blood samples from patients infected with the 2009 H1N1 strain and developed antibodies in cell culture. Some of the antibodies were broadly protective and could provide protection from the H1N1 viruses that circulated over the past 10 years in addition to the 1918 pandemic flu virus and even avian influenza or bird flu (H5N1).
The antibodies protected mice from a lethal viral dose, even 60 hours post-infection.
Some of the antibodies stuck to the â€œstalkâ€ region, or hemagglutinin (H in H1N1) protein part of the virus. Because this part of the virus doesnâ€™t change as much as other regions, scientists have proposed to make it the basis for a vaccine that could provide broader protection. The antibodies could guide researchers in designing a vaccine that gives people long-lasting protection against a wide spectrum of flu viruses.
The paperâ€™s first author, Emory School of Medicineâ€™s Jens Wrammert, PhD, says â€œOur data shows that infection with the 2009 pandemic influenza strain could induce broadly protective antibodies that are very rarely seen after seasonal flu infections or flu shots. These findings show that these types of antibodies can be induced in humans, if the immune system has the right stimulation, and suggest that a pan-influenza vaccine might be feasible.”