Pigs are natural hosts for influenza viruses that can infect humans, in particular the 2009 and, going way back, 1918 H1N1 flu strains. So to understand how influenza infections spread in the body, biochemists and virologists look at pigs.
Biochemistry chair Rick Cummings’ group has a paper in PNAS this week examining the carbohydrates or glycans on the surfaces of pig lung cells, using their “shotgun glycomics” library approach. MMG graduate student Lauren Byrd-Leotis is the first author.
“The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis,” the team reports.
The scientists in the lab of Richard Compans, PhD, professor of microbiology and immunology at Emory, are hard at work, imagining the unimaginable: A time when patients can self-administer flu vaccines. A time when vaccination does not require exposure to inactive viruses. A time when a universal vaccine could protect from all varieties of influenza: swine, avian, seasonal and strains still emerging.
Richard Compans, PhD (right), with colleague Mark Prausnitz, PhD, from Georgia Tech
But it’s not just hope that motivates them as they work. Emory’s scientists are fighting the clock against another possible future: a time of pandemic and uncontrollable virus mutation. The recent emergence of H1N1 and H5N1, known colloquially as swine flu and avian flu, have added an even greater sense of urgency to their task.
“The H5N1â€”the virus derived from avian speciesâ€”has a 60 percent mortality,” says Emory microbiologist Sang-Moo Kang, PhD. Yet that strain of influenza hasn’t resulted in many human deaths, because, so far, avian flu spreads only to humans who are in contact with infected birds.
Dr. Carlos del Rio possesses a keen view of how the novel H1N1 virus emerged last spring. Del Rio was in Mexico as the virus established itself south of the border. Its rapid, far-reaching spread marked the first influenza pandemic of the 21st century.
During Emoryâ€™s fifth annual predictive health symposium, “Human Health: Molecules to Mankind,” del Rio discussed his experiences in Mexico, what weâ€™ve learned, and what novel H1N1 has to do with predictive health.Â View a video of his presentation and five lessons learned.Â
Only a day after the virus was identified, on April 23, Mexican authorities closed schools, called off sporting events, and canceled religious gatherings. Known as â€œsocial distancing,â€ these actions led to a decrease in cases, an important lesson, says del Rio. The public knew what to do, they were cooperative, and whatâ€™s more, they applied a lot of peer pressure when it came to hand washing and sneezing hygiene.
Another lesson learned: preparation paid off. Anticipating a pandemic, The World Health OrganizationÂ had earlier mandated that countries draw up influenza pandemic plans. â€œThose plans were incredibly helpful in getting people to work together, communicate, and know what to do,â€ says del Rio.Â Interestingly, the plans in Mexico and the United States were aimed at a virus projected to originate from an avian source from southeastern Asia. â€œIt was not developed for a swine virus coming from inside the country,â€ explained del Rio.
Novel H1N1, even though itâ€™s thought of as a swine virus is in fact only about 47% swine–30% from North American swine and 17% from Eurasian swine. The virus also contains human and avian strains. Thatâ€™s important, says del Rio, because the characteristics of its genes determine how symptoms, susceptibility, and immunity manifest themselves.
â€œWhat weâ€™re seeing nowadays is the new strain has crowded out the seasonal influenza virus,â€ he says. Thus far, most of the deaths from novel H1N1 have been in children, young adults, and pregnant women. â€œThe people who are dying are a very different group than in previous flu seasons,â€ says del Rio.Â
Carlos del Rio, MD
Del Rio says a lot was learned early on about the novel virus thanks to frequent and transparent international communication. This flu pandemic is really the first to occur in this era of 24-hour newscasts and the Internet. So thereâ€™s a challenge for health workers: how do you continue to communicateÂ in an effective way. â€œOne thing you say one day may be contradicted the next day because you have new information. How do you make people understand that you werenâ€™t lying to them before, but you have updated information and that information is continuously changing.”
In trying to predict whatâ€™s in store for the current flu pandemic, researchers are looking back at past pandemics. Last century, there were three major flu pandemics. The largest and most important was the 1918 pandemic.
â€œA couple of things that happened back then are very important: one was there was a second wave that was actually much more severe and much more lethal than the first one.â€ says del Rio. â€œAnd over the summer, the virus actually changed. It started very much like it did this time. It started in the spring and then we had a little blip, and then we had a big blip in the second wave, and then almost a third wave. So, clearly influenza happens in waves, and weâ€™re seeing the same thing happening this time around.â€
RSPH students Nick Schaad (left) and Michael Marrone
Nick Schaad was among the students authorized to help man the CDCâ€™s Emergency Operations Center at the height of the novel H1N1 outbreak. Once the CDC began to identify influenza clusters, students began conducting phone surveys.
Schaad says he was involved in the St. Francis prep school survey in New York. Students and staff member who were sick with any flu-like symptoms were identified. The team called them and asked about the size of their household, what they might have done to protect themselves, and any recent travel. The goal was to learn as much possible about H1N1 in advance of the fall flu season.
Like the students they teach, RSPH faculty became engaged in the H1N1 epidemic. Last spring, Emory physician and microbiologist Keith Klugman, MD, PhD, was recruited to join the CDCâ€™s Team B, which includes experts from outside the CDC to quickly review and inform the agencyâ€™s efforts. CDC created Team B in the early 2000s to cope with the growing complexity of public health emergencies.
Keith Klugman, MD, PhD
Klugman says his role included the bacterial complications of influenza. Evidence from 1918, notes Klugman, clearly shows that the great majority of deaths were due to bacterial complications of the flu. In other words, the flu itself could occasionally cause death on itss own. But it caused death mostly by facilitating a synergistic lethality between itself and bacteria.
Although much has changed since 1918, the bacteria that caused so many deaths still exist but are susceptible to antibiotics.
Klugman notes the evolution of the flu. He says so far it’s generally been moderate. However, by mixing with the circulating flu in the Southern Hemisphere, it could mutate and become resistant to the first line of flu drugs. It could also become more severe. Says Klugman, â€œWe must remain ever vigilant.â€
An outbreak of measles in the state of Washington last year sickened 19 children. Of those who fell ill, 18 had something in commonâ€”they were not vaccinated.
Saad Omer aims to increase vaccine compliance to prevent childhood diseases.
For Emory Rollins School of Public Health researcher Saad Omer, the Washington outbreak is a perfect example of the effect on an entire community when individuals are unimmunized. His research aims to shed light on ways to encourage increased vaccine compliance for adults and their children.
Omer says vaccine-preventable diseases such as measles, influenza, and pertussis often start among persons who forego vaccinations, spread rapidly within unvaccinated populations, and also spread to other subpopulations.
In a recent New England Journal of Medicinearticle, Omer and his colleagues reviewed evidence from several states showing that vaccine refusal due to nonmedical reasons puts children in communities with high rates of refusal at higher risk for infectious diseases such as measles and whooping cough.
Even children whose parents do not refuse vaccination are put at risk because “herd immunity” normally protects children who are too young to be vaccinated, who can’t be vaccinated for medical reasons, or whose immune systems do not respond sufficiently to vaccination.
Research findings indicate that everyone who lives in a community with a high proportion of unvaccinated individuals has an elevated risk of developing a vaccine-preventable disease.
Read more about Omerâ€™s research on vaccine refusals in the fall 2009 issue of Public Health magazine.
Omer also discusses the importance of vaccinating against the H1N1 virus in an Oct. 16 article in The New York Times.
Clinical trials are underway at Emory and Children’s Healthcare of Atlanta testing an investigational H1N1 flu vaccine along with the seasonal flu vaccine. Emory will enroll about 100 children, ages six months to 18 years, and up to 650 children nationally will participate in the study.
The study will look at the safety of and measure the body’s immune response to the H1N1 flu vaccine. In addition, it will help determine how and when the vaccine should be given with the seasonal flu vaccine to make it most effective.
Another important factor is learning if there are any potential problems by giving the vaccines together, such as whether one vaccine will undermine the protective power of the other.
The answer is important because experts are predicting that both strains of flu will circulate this fall and winter.
Keyserling says that because children and young adults are considered among the most vulnerable populations for new and emerging strains of influenza, such as the current H1N1 pandemic, it is critically important that testing for a vaccine is quick and efficient.
Experts on H1N1 influenza are collaborating all across the country to learn more about the virus and how to prevent its transmission. In a race against time, Emory studies are taking place in the lab and in human clinical trials to help find a vaccine that can be used in the near weeks to come.
Recently, Emoryâ€™s Jeff Koplan, MD, vice president for global health and past CDC director, participated in a Breakthroughs panel sponsored by Big Think, Pfizer and Discover to discuss the latest issues in pandemic and genomic science, fields that have not only made big headlines recently but also promise to be two of the most pressing topics in global science and medicine in coming years.
Jeffrey P. Koplan, MD, MPH
The panel focused on the real-time, round-the-clock scientific mission to understand the history, significance, and future of the new strain of flu that emerged suddenly this spring. Panelists included Koplan; Barry Bloom, Joan L. and Julius H. Jacobson Professor of Public Health at Harvard; Peter Palese, chairman of the microbiology department at Mt. Sinai Medical Center; and Michael Worobey, ecologist and evolutionary biologist at the University of Arizona.
View: Superbug – Are We Prepared for The Next Great Plague?
Emory began signing up several hundred interested volunteers several weeks ago for a clinical trial of the H1N1 vaccine along with the seasonal flu vaccine. About 170 adults have now been vaccinated in the trial, which will last about nine weeks and involve several vaccinations and blood tests. A clinical trial testing the H1N1 vaccine in children will begin at Emory and Children’s Healthcare of Atlanta in the next few days, followed by another adult clinical trial adding an adjuvant to the H1N1 vaccine.
In addition, a multi-pronged attack against the H1N1 virus by Emory researchers is using a new method of rapidly producing highly targeted monoclonal antibodies to develop a diagnostic test as well as a temporary therapy to stave off the H1N1 virus. The antibodies, which can be isolated from a small amount of the blood of humans infected with the virus, could be targeted against H1N1 and rapidly reproduced to detect or attack the virus.
Today Emory researchers began vaccinating volunteer participants in the first of several planned clinical trials of a new H1N1 vaccine. A morning press briefing attended by Atlanta and national media provided Emory a platform to inform the public.
The clinical trials are expected to gather critical information that will allow the National Institutes of Health to quickly evaluate the new vaccines to determine whether they are safe and effective in inducing protective immune responses. The results will help determine how to begin a fall 2009 pandemic flu vaccination program.
Emory began signing up several hundred interested volunteers about two weeks ago and has been screening the volunteers to make sure they fit certain criteria. Volunteers will receive their first vaccinations over the first week of the trial and will return several times over the course of nine weeks to receive additional vaccinations and blood tests.
H1N1 clinical trial volunteer
The clinical trials are in a compressed timeframe because of the possible fall resurgence of pandemic H1N1 flu infections that may coincide with the circulation of seasonal flu strains.
A new method of rapidly producing highly targeted monoclonal antibodies could soon be used to rapidly diagnose H1N1 influenza. Just a month after vaccinating people with a seasonal flu vaccine, the researchers were able to use just a few tablespoons of the vaccinated individuals’ blood to generate antibodies against that specific strain of flu. The research was published last spring in Nature.
The scientists believe their discovery could be applied to any infectious disease. By using a few drops of blood from infected people, they could isolate antibodies to rapidly diagnose a newly emerging flu strain such as H1N1.
There are many variations of H1N1, says Rafi Ahmed, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, but this technology could be used to identify a very specific strain, such as the one weâ€™re dealing with in the current pandemic. The diagnostic tests available now are not specific to any particular H1N1 strain.
Ahmed and his colleagues, including postdoctoral fellow Jens Wrammert, and Patrick Wilson from the University of Chicago, hope their work will lead to a new, specific test for H1N1 within the next several months.
Conventional methods of making human monoclonal antibodies are time-consuming and laborious, says Ahmed. For example, one method involves sifting through human B cells â€”white blood cells that make human antibodiesâ€”and then looking for specific cells that make the right antibodies.
Not only is the new method quicker and less cumbersome, it could be applied to almost any infectious disease. In any kind of emerging infection, speed is essential, says Ahmed.
To listen to Ahmed describe the new monoclonal antibody method, listen to Emoryâ€™s Sound Science podcast.