In recent years, scientists have studied the possibility of using engineered human adenoviruses as vaccines against diseases such as HIV, tuberculosis, and malaria. In this approach, adenoviruses, which commonly cause respiratory-tract infections, are rendered relatively harmless before they are used as vectors to deliver genes from pathogens, which in turn stimulate the body to generate a protective immune response.
In a new study of four adenovirus vectors, researchers from The Wistar Institute show that a reportedly rare human adenovirus, called AdHu26, is not so rare, after all, and would thus be unlikely to be optimal as a vaccine carrier for mass vaccination. As previous research has shown, a viral vector may be ineffective if the virus it is based on is common in a given population. According to the Wistar scientists, their study also supports the use of chimpanzee adenoviruses as vaccine vectors, since humans have little exposure to these viruses. Their findings were published online, ahead of print, in the Journal of Virology.
"Despite previous reports to the contrary, we find that AdHu26 commonly infects people, particularly those in Sub-Saharan Africa, the very people for whom the need for novel vaccine strategies is most dire," said senior author Hildegund C. J. Ertl, M.D., Wistar professor and director of The Wistar Institute's Vaccine Center. "HIV, malaria, and other infectious diseases take a tremendous toll in the developing world, especially in Sub-Saharan Africa, and a vaccine platform that could be used in those regions could save the lives of millions."
Scientists believe that prior immunity to human adenoviruses is what led, in part, to the failure in 2007 of the STEP trial, a large vaccine trial in the US and other countries that used an adenovirus vector as the basis for an HIV vaccine.
In the current study, Ertl and her colleagues analyzed blood samples collected from people at seven sites around the world, including Thailand, the United States, and five sub-Saharan African nations. They tested the samples to see if they contained neutralizing antibodies and responsive immune cells when exposed to AdHu26 and AdHu5, the virus used in the STEP trial. Surprisingly, neutralizing antibodies to AdHu26 were very prevalent in blood.
According to Ertl, adenoviruses are still good vaccine vectors, just not necessarily human adenoviruses. In addition to testing AdHu5 and AdHu26, the Wistar scientists also tested two adenoviruses that originated in chimpanzees, called AdC6 and AdC7. As expected, neutralizing antibodies were far less likely to be detected in human samples. Mouse studies of all four vectors demonstrated that they were similar in their ability to generate cellular immune responses.
"This study also confirms our current line of research that suggests engineered chimpanzee adenovirus vectors could be superior to related, native human adenoviruses," Ertl said. "Both human and chimpanzee adenoviruses function in similar ways, but the simple benefit is that humans are rarely exposed to adenoviruses of chimpanzee origin."
The Ertl laboratory is currently developing an HIV vaccine utilizing chimpanzee adenoviruses.
Along with senior author Ertl, co-authors from the Ertl laboratory include senior staff scientists Zhi Quan Xiang, M.D., and Xiang Zhou, M.D.; staff scientist Dongming Zhou, M.D., Ph.D.; research technician Yan Li; research assistant Ang Bian; and visiting scientists Heng Chen and Raj Kurupati, Ph.D. Co-authors also include Michael Betts, Ph.D.; Natalie Hutnick; Sally Yuan, Ph.D.; and Clive Gray, Ph.D.; of the University of Pennsylvania School of Medicine's Department of Microbiology; Jennifer Serwanga, Ph.D., of the National Institute for Communicable Diseases in South Africa; and Betty Auma, Ph.D.; and Pontiano Kaleebu, Ph.D.; of the Uganda Research Unit on AIDS in Uganda.
Funding for this study was provided through grants from the National Institutes of Health.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today's Discoveries – Tomorrow's Cures. On the Web at www.wistar.org
Greg Lester | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy