Paper of the Month: New peroxide-based inactivation approach to vaccines looks promising

"This is an exciting technological advance that offers great promise for the future development of stronger, more efficacious vaccines against viral pathogens."

- Mary Stenzel-Poore, PhD
Senior Associate Dean for Research

This month's featured paper is from the laboratory of Dr. Mark Slifka, and is titled, "Development of a new hydrogen peroxide–based vaccine platform." It was published in the journal Nature Medicine. The research in this paper was conducted by investigators at the Oregon National Primate Research Center, the OHSU Department of Molecular Microbiology & Immunology and from Najít Technologies, in Beaverton, Ore.

Dr. SlifkaDespite efforts of their eradication, infectious diseases spread by mosquitoes remain a significant cause of global health, economic, and social problems.

West Nile virus, for example, is endemic throughout the United States and spreading through Europe. Yellow fever, once deemed among the most dangerous infectious diseases in the world, continues to be a problem in South America and Africa. And Dengue, found in more than 110 countries, is responsible for nearly 50 million infections every year. Complications from these diseases can lead to severe illness, hospitalization, or death.

Scientists in the Mark Slifka Laboratory (funded to develop new vaccines against West Nile virus, yellow fever virus, and dengue) are researching ways to prepare safer and more effective vaccines to fight these infections, thereby reducing the global burden caused by these diseases, including medical costs and loss of life.

The team's focus is on a novel peroxide-based inactivation approach, which has performed very well in preliminary animal models.

"Our research has demonstrated that viruses can be efficiently inactivated by hydrogen peroxide but without major damage to immunogenic epitopes," said paper author Mark Slifka, Ph.D., professor and senior scientist at the Oregon National Primate Research Center with an adjunct appointment in the Department of Molecular Microbiology & Immunology. To determine if it could be used as a vaccine platform, the investigators tested it in 3 independent animal models. "We found that we could protect mice against both chronic viral infection as well as lethal viral infection, which is very exciting."

Although most vaccines are very safe, Dr. Slifka pointed to the yellow fever vaccine as an example of vaccines that "have less than favorable" safety profiles.

"The current yellow fever vaccine is responsible for 1 to 2 deaths per million doses administered including fatalities among young, otherwise healthy adults," said Dr. Slifka. "The vaccine has not been recommended in infants since the 1960's due to high rates of viral encephalitis." More recently, viscerotropic disease (with ~50% mortality) has been observed in the elderly at an alarming rate of approximately 1 per 50,000 doses.There is currently no vaccine available for these vulnerable populations.

Dr. Slifka is hoping to fill that void by providing a safe and effective inactivated yellow fever vaccine that can be used in all individuals without the risks of the current live virus vaccine.

The team's research introduces an entirely new approach to vaccine development. In the past, most inactivated vaccines were produced by killing viruses with chemicals such as formaldehyde or betapropiolactone but no one, said Dr. Slifka, has tried peroxide (an oxidizing agent) to kill viruses because it was thought to be far too damaging and therefore it would never work.

"We took a gamble in trying it (peroxide), and were surprised to find that it works very well and induces protective immunity in each model system that we have tested," he said.The team's goal is to get these new vaccines into the clinic. "We have NIH funding to produce clinical-grade vaccine material under cGMP conditions and we hope to initiate our first Phase I clinical trials on West Nile virus and yellow fever within the next 1-2 years with our dengue vaccine trials hopefully beginning within 4-5 years," said Dr. Slifka.

Of the three diseases, only yellow fever has an approved commercial vaccine licensed for use in the United States.

Read Development of a new hydrogen peroxide–based vaccine platform, published in Nature Medicine, paper here.
Picture above: Mark Slifka, Ph.D.

Vaccination Nation? Separating Fact from Fiction

Mark Slifka, PhD, will be a featured speaker at the Marquam Hill Lecture series on Feb 21, 2013. His presentation will focus on what science tells us about vaccines to help you make an informed decision about vaccines for you and your children.

*Paper Authors

Ian Amanna, Ph.D., Najít Technologies

Hans-Peter Raué, Ph.D., Oregon National Primate Research Center

Mark Slifka, Ph.D., Oregon National Primate Research Center and OHSU Department of Molecular Microbiology & Immunology


The School of Medicine newsletter spotlights a recently published faculty research paper in each issue. The goals are to highlight the great research happening at OHSU and to share this information across departments, institutes and disciplines. The monthly paper summary is selected by Associate Dean for Basic Science Mary Stenzel-Poore, PhD.

More Published Papers

The entire list of OHSU papers published this month is here.