New findings provide insight into how the Nipah and Hendra viruses attack cells, as well as the immune responses that try to combat this epidemic. The findings suggest that multi-pronged strategies to prevent and treat these fatal diseases are essential.
This research is now available in Science as a peer-reviewed paper called First Release, which is now available online.
Both the Nipah virus and Hendra virus are carried by bats native to certain parts of the world. These henipaviruses are important mammals, including humans. The viruses cause brain inflammation and respiratory symptoms. People acquiring either of these diseases have a 50% to 100% chance of succumbing.
A horse vaccine has been approved for use, and a modified version has been used in a human clinical trial.
Horses can spread Hendra, which may be contracted from eating bat-contaminated fruit, through saliva and nasal secretions. A clinically-approved cross-reactive antibody aimed at both Nipah and Hendra viruses has been developed for fifteen individuals who had a high-risk exposure. This antibody has just completed the Phase 1 stage of testing. There are no acceptable vaccinations or therapies for humans against these henipaviruses, except supportive care in the limited hope that the patient can overcome the virus.
New approaches to design life-saving interventions and treatments became even more urgent after a fresh strain of Hendra was discovered a few months ago. Outbreaks of the Nipah virus have occurred almost every year in Bangladesh, as have indigenous people and Pteropus bats in Africa. It''s estimated that 2 billion people live in the world where henipavirus spillovers from bats, or intermediary animal vectors, might be a threat.
David Veesler, an associate professor of biochemistry at the University of Washington, and a Howard Hughes medical investigator, is responsible for studying bat immunity to many dangerous viruses. He conducts molecular structure and function studies of the infectivity machinery in coronaviruses, other related viruses, and henipaviruses. His laboratory also investigates antibody and virus interactions that provide clues for designing antivirals and vaccinations for these two families of viruses.
Zhaoqian Wang, a UW graduate student in biochemistry, has been named the author.Christopher Broders has labcollaborated on the research at the Uniformed Services University and the Henry M. Jackson Foundation for Military Medicine.
Nipah and Hendra viruses enter into cells through attachment and fusion glycoproteins, which work in a coordinated manner. These glycoproteins are the key targets for the antibody defense system.
In vitro electroelectron imaging, scientists figured out the structure of a key component of the Nipah viruses infection mechanism in an interaction with a fragment of a broadly neutralizing antibody. Moreover, a combination or cocktail of antibodies worked better together to disarm Nipah viruses. Similar synergistic effects were observed in a set of antibodies against Hendra viruses. This combining of forces also helped keep escape mutants from developing to disrupt the antibody response.
In experiments conducted with a critical section of the Nipah virus infection machinery, vital information was provided. The study uncovered which area of the virus receptor binding protein was dominant in eliciting an immune response.
The researchers said that nothing was found on the structure of a critical portion of henipaviruses responsible for generating antibody response, called the HNV G protein. This lack of information was a challenge to understanding immunity and to improve the design of vaccination candidates.
Science may be moving towards a new and improved vaccination model as soon as the researchers have discovered the 3D structure and some of the conformational dynamics of the HNV G protein.
One of the four heads in the attachment structure, a neck and a head, gives the viral structure the ability to re-orient the head domain to engage with the host receptor.
The design then adopts a unique two heads up and two heads down conformation that is different from any other paramyxovirus attachment glycoprotein. These are often caused by respiratory droplets, which include measles, diarrhea, distemper, parainfluenza, and the henipavirus infections that have recently crossed from animals to humans.
The scientists studied two animals who were immunized with the Nipah virus attachment protein G, which was shown to be the main, if not exclusive target, of the immunization-induced antibody neutralization. Despite the use of the full tetramer, this indicated that the antibody response narrowed in on the receptor-binding area.
The authors indicated that these findings will provide a roadmap for developing future-generation vaccine candidates with improved stability and immunogenicity. They envision a design approach similar to that used for new-generation SARS-CoV-2 and respiratory syncytial virus candidates. A mosaic of head antigens would be presented to the body in a multivalent array. Large quantities of vaccine may also be reduced.