A team of researchers has developed a new vaccine design strategy that could confer improved immunity against certain viruses, including those that cause AIDS, the flu, and COVID-19. Using this technique, the scientists attached proteins from the surface of a virus, called antigens, to custom-made protein nanoparticles. This approach enables an unprecedented level of control over the molecular configuration of the resulting vaccine. This research, which includes pre-clinical evaluation of some initial vaccines in animals, is detailed in three new papers published Aug, 4. The first paper, published in the journal eLife, describes the overall vaccine design strategy and how it was used to create vaccine candidates for three important viruses: HIV; respiratory syncytial virus, or RSV; and influenza.
"One of the things we found in this study was that putting the same viral antigen onto different nanoparticles altered which regions antibodies can see. This can be used to bias the immune response toward certain regions of an antigen that confer greater protective immunity," said lead author George Ueda, a translational postdoctoral scholar at the UW Medicine Institute for Protein Design.
The second paper, published in PLOS Pathogens, looks at how one of the new HIV vaccine nanoparticles performed in rabbits. A team led by Aleks Antanasijevic and Andrew Ward at Scripps Research found that repeated immunization of the vaccine resulted in a higher proportion of neutralizing antibodies compared to immunization with the same antigen not displayed on a custom-made nanoparticle.
The third paper, published in npj Vaccines, looks at how one of the HIV vaccine nanoparticles circulates through the body of rhesus macaques. A team led by Jacob Martin and Darrell Irvine at MIT found that after three days, it became concentrated in lymph node tissues, which is where B cells learn how to fight infection. This may account for the observed enhanced immunity, according to the researchers.
"Simply injecting an antigen is not necessarily enough to confer a protective immune response. Our goal was to create new protein-based vaccines that mimic the repetitive and spiky shape of a virus because that can drive a more protective immune response. What we found in this last study was that the nanoparticle vaccines are also retained better in lymph nodes than antigen alone." said Ueda.
The team chose to focus on HIV, RSV, and influenza because those viruses all contain surface proteins with similar shapes calle trimers. The virus that causes COVID-19 also contains a trimeric surface protein. Efforts are underway at UW Medicine and at the National Institutes of Health Vaccine Research Center to develop nanoparticle vaccines against COVID-19 by using this new strategy.
"We have found that the two-component nanoparticles we've been designing can be used to improve the potency of antigens from a number of important pathogens, including SARS-CoV-2. We're convinced that they are a robust and versatile platform for designing nanoparticle vaccines," said Neil King, assistant professor of biochemistry at the UW School of Medicine and a researcher at the UW Medicine Institute for Protein Design.
This collaborative research was led by UW Medicine, Scripps Research, and the Koch Institute for Integrative Cancer Research at MIT. It also included researchers from Cornell University, Emory University, University of Amsterdam, University of Southampton, the Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, the Lawrence Berkeley Laboratory, and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
This work was supported by the Bill and Melinda Gates Foundation and the Collaboration for AIDS Vaccine Discovery (OPP1156262, OPP1120319, OPP1115782, OPP1111923, OPP1132237, and OPP1196345); the National Institute of Allergy and Infectious Diseases Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (UM1AI100663), Center for HIV/AIDS Vaccine Development (UM1AI144462, P01 811 AI110657, R01 AI36082, R01AI073148, and R01AI128836); and by the National Science Foundation ( NSF CHE 1629214); and by The Audacious Project; and by the Howard Hughes Medical Institute. This work was also supported by the European Union's Horizon 2020 research and innovation program (681137). This work was partially funded by the International AIDS Vaccine Initiative (IAVI) with the support of USAID, Ministry of Foreign Affairs of the Netherlands, and the Bill & Melinda Gates Foundation. A full list of IAVI donors is available at www.iavi.org.
Written by Ian Haydon, Institute for Protein Design.
Scientific papers mentioned in this news release:
Lead authors: George Ueda and Aleks Antanasijevic
Published: August 4, eLife
Structural and Functional Evaluation of De Novo-designed, Two-component Nanoparticle Carriers for HIV ENV Trimer Immunogens
Lead author: Aleks Antanasijevic. Senior author: Andrew Ward
Published: August 4, PLOS Pathogens
Targeting HIV ENV Immunogens to B Cell Follicles in Non-human Primates through Immune Complex or Protein Nanoparticle Formulations
Lead authors: Jacob T. Martin, C.A. Cottrell, and Aleks Antanasijevic. Senior author: Darrell Irvine
Published: August 4, npj Vaccine
