Compound discovered that boosts effect of vaccines against HIV and flu

ScienceDaily (Aug. 26, 2012) — Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.

An 'adjuvant' is a substance added to a vaccine to enhance the immune response and offer better protection against infection.

The Oxford University team, along with Swedish and US colleagues, have shown that a type of polymer called polyethyleneimine (PEI) is a potent adjuvant for test vaccines against HIV, flu and herpes when given in mice.

The researchers were part-funded by the UK Medical Research Council and report their findings in the journal Nature Biotechnology.

Mice given a single dose of a flu vaccine including PEI via a nasal droplet were completely protected against a lethal dose of flu. This was a marked improvement over mice given the flu vaccine without an adjuvant or in formulations with other adjuvants.

The Oxford researchers now intend to test the PEI adjuvant in ferrets, a better animal model for studying flu. They also want to understand how long the protection lasts for. It is likely to be a couple of years before a flu vaccine using the adjuvant could be tested in clinical trials in humans, the researchers say.

'Gaining complete protection against flu from just one immunisation is pretty unheard of, even in a study in mice,' says Professor Quentin Sattentau of the Dunn School of Pathology at Oxford University, who led the work. 'This gives us confidence that PEI has the potential to be a potent adjuvant for vaccines against viruses like flu or HIV, though there are many steps ahead if it is ever to be used in humans.'

HIV, flu and herpes are some of the most difficult targets to develop vaccines against. HIV and flu viruses are able to change and evolve to escape immune responses stimulated by vaccines. There aren't any effective vaccines against HIV and herpes as yet, and the flu vaccine needs reformulating each year and doesn't offer complete protection to everyone who receives it. Finding better adjuvants could help in developing more effective vaccines against these diseases.

Most vaccines include an adjuvant. The main ingredient of the vaccine -- whether it is a dead or disabled pathogen, or just a part of the virus or bacteria causing the disease -- primes the body's immune system so it knows what to attack in case of infection. But the adjuvant is needed as well to stimulate this process.

While the need for adjuvants in vaccines has been recognised for nearly 100 years, the way adjuvants work has only recently been understood. The result has been that only a small set of adjuvants is used in current vaccines, often for historical reasons.

The most common adjuvant by far is alum, an aluminium-containing compound that has been given in many different vaccines worldwide for decades. However, alum is not the most potent adjuvant for many vaccine designs.

'There is a need to develop new adjuvants to get the most appropriate immune response from vaccines,' says Professor Sattentau, who is also a James Martin Senior Fellow at the Oxford Martin School, University of Oxford.

The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity.

When included in a vaccine with a protein from HIV, flu or herpes virus, mice subsequently mounted a strong immune response against that virus. The immune response was stronger than with other adjuvants that are currently being investigated.

The team also showed that PEI is a potent adjuvant in rabbits, showing the effect is not just specific to mice and could be general.

Another potential advantage of PEI is that it works well as an adjuvant for 'mucosal vaccines'. These vaccines are taken up the nose or in the mouth and absorbed through the mucus-lined tissues there, getting rid of any pain and anxiety from a needle. Mucosal vaccines may also be better in some ways as mucosal tissues are the sites of infection for these diseases (airways for respiratory diseases, genital mucosa for HIV and herpes).

Professor Sattentau suggests that: 'In the best of all possible worlds, you could imagine people would have one dose of flu vaccine that they'd just sniff up their nose or put under their tongue. And that would be it: no injections and they'd be protected from flu for a number of years.

'It's just a vision for the future at the moment, but this promising adjuvant suggests it is a vision that is at least possible.'

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The above story is reprinted from materials provided by University of Oxford, via EurekAlert!, a service of AAAS.

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Multiple sclerosis-like disease discovered in monkeys

ScienceDaily (June 28, 2011) — Researchers at Oregon Health & Science University have discovered a naturally occurring disease in monkeys that is very much like multiple sclerosis in humans -- a discovery that could have a major impact on efforts to understand the cause of multiple sclerosis.

The disease that the researchers discovered in monkeys at OHSU's Oregon National Primate Research Center is associated with a herpes virus that could give significant clues into how multiple sclerosis develops in humans. MS researchers have long believed that a type of herpes virus may trigger multiple sclerosis in people who are genetically susceptible to the disease.

The OHSU researchers' findings were published online in the Annals of Neurology.

"These findings could have a huge impact on our understanding of MS and could be a landmark in someday developing more effective treatments for the disease, or even methods to prevent the onset of MS," said Scott Wong, Ph.D., senior author of the study and a scientist at the Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center.

Both elements of the OHSU discovery are important for MS researchers.

Before the OHSU findings, researchers had been able to study MS-like diseases in nonhuman primates only after the disease had been artificially induced. A naturally occurring disease, such as the one discovered at OHSU, can give researchers many more clues into the causes and development of the disease.

"Now, we may be able to tease apart what's triggering the onset of the disease," Wong said.

And the fact that the disease, found in a small percentage of the Japanese macaques at OHSU each year, came from a herpes virus could prove hugely important to MS researchers worldwide. Researchers can now search for a similar virus in MS patients.

The cause of MS, which affects about 400,000 people in the United States, is unknown. But researchers have long believed that a virus, possibly a herpes virus, might trigger the disease in people who are genetically susceptible.

"Understanding how this herpes virus causes the MS-like disease in the monkeys will give us important new knowledge -- and drive new research that could lead to significant advancements in finding and preventing the virus that might cause MS," said Dennis Bourdette, M.D., a co-author of the study, director of the Multiple Sclerosis Center of Oregon and professor and chairman of the OHSU Department of Neurology.

From 1986 through 2010, 56 of the Japanese macaque monkeys at the Oregon National Primate Research Center at OHSU spontaneously developed paralysis in their hind limbs, along with other symptoms. The monkeys were humanely euthanized because they could not have been returned to the monkey colony safely. Researchers later did necropsies on the their bodies and performed MRI scans on eight of the animals.

That work and other testing allowed researchers to discover that an MS-like disease called Japanese macaque encephalomyelitis was causing the paralysis. While the disease typically afflicted young adult animals, it also was present in juveniles and older animals, and was present in both males and females.

About 1 to 3 percent of the more than 300 Japanese macaques at the primate center develop the disease each year, according to the researchers.

With this discovery, MS researchers now will be able to move toward trying to prevent or treat the virus in monkeys, which might help scientists make progress in treating MS in humans.

In addition to Wong and Bourdette, co-authors of the study include Michael Axthelm, D.V.M., Ph.D., of the Vaccine and Gene Therapy Institute; William Rooney, Ph.D., of OHSU's Advanced Imaging Research Center; and Larry Sherman, Ph.D., of the Oregon National Primate Research Center.

The research was supported by the National Institutes of Health, the Research Enrichment Award Program of the Department of Veterans Affairs Biomedical Laboratory Research and Development, the OHSU Multiple Sclerosis Center, and the United States Department of Defense. The study is titled "Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease."

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Journal Reference:

Michael K. Axthelm, Dennis N. Bourdette, Gail H. Marracci, Weiping Su, Elizabeth T. Mullaney, Minsha Manoharan, Steven G. Kohama, Jim Pollaro, Ellen Witkowski, Paul Wang, William D. Rooney, Lawrence S. Sherman, Scott W. Wong. Japanese macaque encephalomyelitis: A spontaneous multiple sclerosis-like disease in a nonhuman primate. Annals of Neurology, 2011; DOI: 10.1002/ana.22449

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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