Posts Tagged ‘vaccine’

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Researchers have identified a brand new ‘micro-organ’ inside the immune system of mice and humans – the first discovery of its kind for decades – and it could put scientists on the path to developing more effective vaccines in the future.

Vaccines are based on centuries of research showing that once the body has encountered a specific type of infection, it’s better able to defend against it next time. And this new research suggests this new micro-organ could be key to how our body ‘remembers’ immunity.

The researchers from the Garvan Institute of Medical Research in Australia spotted thin, flat structures on top of the immune system’s lymph nodes in mice, which they’ve dubbed “subcapsular proliferative foci” (or SPFs for short).

These SPFs appear to work like biological headquarters for planning a counter-attack to infection.

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Immune cells gathering at the SPF, with the purple band showing the SPF surface.

These SPFs only appear when the mice immune systems are fighting off infections that have been encountered before.

What’s more, the researchers detected SPFs in human lymph nodes too, suggesting our bodies react in the same way.

“When you’re fighting bacteria that can double in number every 20 to 30 minutes, every moment matters,” says senior researcher Tri Phan. “To put it bluntly, if your immune system takes too long to assemble the tools to fight the infection, you die.”

“This is why vaccines are so important. Vaccination trains the immune system, so that it can make antibodies very rapidly when an infection reappears. Until now we didn’t know how and where this happened.”

Traditional microscopy approaches analyse thin 2D slices of tissue, and the researchers think that’s why SPFs haven’t been spotted before – they themselves are very thin, and they only appear temporarily.

In this case the team made the equivalent of a 3D movie of the immune system in action, which revealed the collection of many different types of immune cell in these SPFs. The researchers describe them as a “one-stop shop” for fighting off remembered infections, and fighting them quickly.

Crucially, the collection of immune cells spotted by the researchers included Memory B type cells – cells which tell the immune system how to fight off a particular infection. Memory B cells then turn into plasma cells to produce antibodies and do the actual work of tackling the threat.

“It was exciting to see the memory B cells being activated and clustering in this new structure that had never been seen before,” says one of the team, Imogen Moran.

“We could see them moving around, interacting with all these other immune cells and turning into plasma cells before our eyes.”

According to the researchers, the positioning of the SPF structures on top of lymph nodes makes them perfectly positioned for fighting off infections – and fast.

They’re strategically placed at points where bacteria would invade, and contain all the ingredients required to keep the infection at bay.

Now we know how the body does it, we might be able to improve vaccine techniques – vaccines currently focus on making memory B cells, but this study suggests the process could be made more efficient by also looking at how they transform into plasma cells through the inner workings of an SPF.

“So this is a structure that’s been there all along, but no one’s actually seen it yet, because they haven’t had the right tools,” says Phan.

“It’s a remarkable reminder that there are still mysteries hidden within the body – even though we scientists have been looking at the body’s tissues through the microscope for over 300 years.”

The research has been published in Nature Communications.

https://www.sciencealert.com/researchers-identify-new-lymph-node-structures-powering-immunity

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Scientists at The Scripps Research Institute (TSRI) have achieved a major milestone toward designing a safe and effective vaccine to both treat heroin addiction and block lethal overdose of the drug. Their research, published today in the journal Molecular Pharmaceutics, shows how a new anti-heroin formulation that is safe in animal models remains stable at room temperature for at least 30 days. As a result, the vaccine is close to being ready for human testing.

“The heroin vaccine is one step closer to clinical evaluation,” says Candy S. Hwang, PhD, first author of the study and a research associate at TSRI.

According to the National Institute on Drug Abuse, 15,446 Americans died from heroin overdose between 2000 and 2016, and the mortality rates are increasing. Heroin abuse has been further fueled by a rise in prescription opioid abuse—studies show that opioid pain reliever users are 40 times more likely to abuse heroin.

The first formulation of the heroin vaccine was developed in 2013 by a team led by Kim D. Janda, PhD, the Ely R. Callaway Jr. Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI. It has been shown to be effective—and safe—in both mouse and non-human primate models.

The vaccine works by training the immune system antibodies to recognize and bind to heroin molecules, blocking the drug from reaching the brain to cause a “high.” Researchers believe that blocking the high of heroin will help eliminate the motivation for many recovering addicts to relapse into drug use.

The heroin molecule does not naturally prompt an antibody response, so researchers attach it to a carrier protein that alerts the immune system to start making antibodies. Scientists also add an ingredient called an adjuvant to the vaccine, which boosts the immune response and makes the vaccine more effective.

Hwang says, “Our goal was to prepare a vaccine that could be advanced to clinical trials. As such, we were looking for the best combination of ‘hapten’ (the heroin molecule), carrier protein and adjuvant to keep the vaccine both stable for transport and storage but still efficacious.”

For the new study, the researchers investigated how 20 different carrier protein/adjuvant combinations worked, including shelf stability based on temperature and storage time and whether the formulation was a liquid or powder.

Their experiments in rodent models showed that the best vaccine formulation contained a carrier protein called tetanus toxoid (TT) and adjuvants called alum and CpG ODN. The discovery that alum worked best as an adjuvant was especially significant since alum is one of the few adjuvants used in vaccines already approved by the U.S. Food and Drug Administration. The researchers also found that there was no difference in how well it worked between the liquid and powder versions of this formulation.

Hwang notes that the best vaccine formulation showed protection against lethal doses of heroin. This is particularly important as many heroin addicts have succumb to overdose and death during their attempts to quit the drug.

With this new study, the researchers have shown that the vaccine is safe and effective in animal models, stable under clinical conditions and reliant on an already-approved adjuvant. The next step is to find a producer to make the vaccine on a large scale.

“We believe that a heroin vaccine would be tremendously beneficial for people who have a heroin substance use disorder but have found difficulty in trying to quit,” says Hwang.

In addition to Hwang and Janda, authors of the study, “Enhancing Efficacy and Stability of an Anti-Heroin Vaccine: Examination of Antinociception, Opioid Binding Profile, and Lethality,” were Paul T. Bremer, Cody J. Wenthur, Beverly Ellis and Bin Zhou of The Scripps Research Institute; and Sam On Ho, SuMing Chiang and Gary Fujii of Molecular Express, Inc.

The study was supported by the National Institutes of Health (grants UH3DA041146, F32AI126628, F32DA043323, R42DA040422 and R44AI094770).

https://www.scripps.edu/news/press/2018/20180213janda.html

By SAM ROBERTS

Julius Youngner, an inventive virologist whose nearly fatal childhood illness destined him to become a medical researcher and a core member of the team that developed the Salk polio vaccine in 1955, died on April 27 at his home in Pittsburgh. He was 96.

His death was confirmed by his son, Dr. Stuart Youngner.

Dr. Youngner was the last surviving member of the original three-man research team assembled by Dr. Jonas Salk at the University of Pittsburgh to address the polio scourge, which peaked in the United States in the early 1950s when more than 50,000 children were struck by it in one year. Three other assistants later joined the group.

Dr. Salk credited his six aides with major roles in developing the polio vaccine, a landmark advance in modern medicine, which he announced on April 12, 1955.

The announcement — that the vaccine had proved up to 90 percent effective in tests on 440,000 youngsters in 44 states — was greeted with ringing churchbells and openings of public swimming pools, which had been drained for fear of contagion. Within six years, annual cases of the paralyzing disease had declined from 14,000 to fewer than 1,000.

By 1979, polio had been virtually eliminated in developed nations.

“I think it’s absolutely fair to say that had it not been for Dr. Youngner, the polio vaccine would not have come into existence,” Dr. Salk’s son, Peter L. Salk, president of the Jonas Salk Legacy Foundation and a visiting professor at the University of Pittsburgh Graduate School of Public Health, said in an email.

While Dr. Youngner, who was 34 at the time, remained at the university and made further advances in virology, he and other members of the team remained embittered that Dr. Salk had not singled them out for credit in his announcement speech.

The printed version was prefaced with the phrase “From the Staff of the Virus Research Laboratory by Jonas E. Salk, M.D.,” and a United Press account quoted him as crediting his original three assistants, who had joined him as early as 1949 — Dr. Youngner, Army Maj. Byron L. Bennett and Dr. L. James Lewis — as well as three others.

“The really important thing to recognize is that the development of the polio vaccine at the University of Pittsburgh was a team effort,” Dr. Peter Salk wrote.

He added, “There is no question that my father recognized the importance of the team, and if there were circumstances in which that wasn’t adequately expressed, I would feel that it needs to be expressed now and very clearly so.”

In 1993, Dr. Youngner crossed paths with Dr. Salk for the first time since Dr. Salk left for California in 1961. According to “Polio: An American Story” (2005), by David M. Oshinsky, Dr. Youngner raised the 1955 announcement speech in confronting Dr. Salk.

“Do you remember whom you mentioned and whom you left out?” the book quoted him as saying to Dr. Salk. “Do you realize how devastated we were at that moment and ever afterward when you persisted in making your co-workers invisible?”

Asked later, though, whether he regretted having worked for Dr. Salk, Dr. Youngner replied: “Absolutely not. You can’t imagine what a thrill that gave me. My only regret is that he disappointed me.”

Dr. Youngner’s contribution to the team was threefold.

He developed a method called trypsinization, using monkey kidney cells to generate sufficient quantities of the virus for experiments and production of the vaccine. He also found a way to deactivate the virus without disrupting its ability to produce antibodies. And he created a color test to measure polio antibodies in the blood to determine whether the vaccine was working.

He later contributed research to understanding interferon as an antiviral agent in the treatment of cancer and hepatitis; to the development (with Dr. Samuel Salvin) of gamma interferon, which is used against certain infections; and to advances that resulted in vaccines for Type A influenza and (with Dr. Patricia Dowling) equine influenza.

“As a direct result of his efforts, there are countless numbers of people living longer and healthier lives,” Dr. Arthur S. Levine, the University of Pittsburgh’s senior vice chancellor for the health sciences and dean of its medical school, said in a statement.

Julius Stuart Youngner was born on Oct. 24, 1920, in Manhattan and raised in the Bronx, where he survived lobar pneumonia, a severe infection of the lungs. His father, Sidney Donheiser, was a businessman. His mother was Bertha Youngner. He took her surname when his parents divorced.

After graduating from Evander Childs High School in the Bronx at 15, he earned a bachelor’s degree in English with a minor in biology from New York University in 1939 and a master’s and doctorate of science in microbiology from the University of Michigan.

Drafted into the Army in World War II, he worked on the Manhattan Project at Oak Ridge, Tenn., and at the University of Rochester, testing the toxicity of uranium salts. He said he learned of the project’s goal of building an atomic bomb only when it was dropped on Japan.

He was working at the National Cancer Institute, part of the National Institutes of Health, when the University of Pittsburgh hired him as an assistant professor in 1949 to assist Dr. Salk. He was a professor of microbiology and medical genetics at the university School of Medicine and chairman of the department of microbiology (biochemistry and microbiology were added later) from 1966 until his retirement in 1989.

His first wife, the former Tula Liakakis, died in 1963. Besides their son, Stuart, a psychiatry and bioethics professor at Case Western Reserve University in Cleveland, Dr. Youngner is survived by his wife, the former Rina Balter; a daughter, Lisa, an artist, also from his first marriage; three grandchildren; and a half brother, Alan Donheiser.

Dr. Youngner’s infectious curiosity, as a colleague characterized it, generated hundreds of scholarly papers and more than 15 patents. He was president of the American Society for Virology from 1986 to 1987.

When he was 7, Dr. Youngner nearly died from the pneumonia he had contracted when bacteria ate through his chest and infected a rib. An effective vaccine for pneumonia and antibiotics would not be invented for nearly two decades.

“So they strapped my legs to a table, and two nuns held my arms and another held my head and they prayed while they operated on me,” he recalled in an oral history interview in the early 1990s with the National Council of Jewish Women. “To this day I can remember the feeling of the saw on that rib.

“Later in life, when I had to have some minor surgery,” he said, “I put it off for years because I was so affected by this episode.”

https://mobile.nytimes.com/2017/05/04/science/julius-youngner-dead-salk-polio-vaccine-researcher.html?_r=0&referer=https://www.google.com/

The biotech company NewLink Genetics in Ames, Iowa is closing in on human trials for an Ebola vaccine.

“From the laboratory to moving these first human trials has moved faster than I’ve ever seen anything move before in my professional career,” said Charles Link, CEO of NewLink Genetics.

Link said they are just a few days away from human testing. During Phase 1 of testing, healthy volunteers will be given the vaccine. Researchers will test to see how safe the vaccine is and what dosage is necessary for an immune reaction.

“With a dangerous virus, you don’t ever use the dangerous virus. You basically use a little snippet of it,” said Link.

Link said that snippet is a surface protein you get from Ebola and assures us there is no Ebola is in the vaccine.

“If you get an immune reaction to the surface protein an then it sees the real Ebola, it will attack it,” said Link.

Once those tests are complete, the company will move into Phase 2 where tests focus on how effective and useful the vaccine is. Those tests will be done in West Africa.

Link said he’s hoping it’ll take less than a year, but there’s no real way of telling when the vaccine will be ready for distribution until test results start coming in.

“We want to shorten the process as much as humanely possible within the bounds of safety and the ethics that’s required to conduct these sorts of studies in healthy volunteers,” said Link.

The Phase 1 of the tests will be conducted at the National Institute of Allergy and Infectious Disease and the Walter Reed Army Medical Center.
Ames Company Close to Ebola Vaccine Trials

http://www.cbs2iowa.com/news/features/top-stories/stories/ames-company-close-ebola-vaccine-trials-30679.shtml