PHARMACEUTICALS
Phage Display-Based Gene Delivery Enables COVID‐19 Vaccine Design
Compiled by John Joseph Parker Contributing Editor
Researchers at Rutgers Cancer Institute of New Jersey , Rutgers New Jersey Medical School ( NJMS ) and the Center for Theoretical Biological Physics ( CTBP ) at Rice University in Houston , Texas , have demonstrated that a technology with favorable biological attributes known as phage display could be a viable platform for the development of new vaccines to protect against COVID‐19 . Findings from the proof-of-concept work were published online in the Proceedings of the National Academy of Sciences ( PNAS ) journal .
Currently approved vaccines against COVID‐19 worldwide include mRNA-based vaccines , non-replicating adenovirus vaccines and an inactivated SARS-CoV-2 vaccine among others . While being broadly effective , these vaccine types suffer many challenges , particularly in rapid large-scale production and distribution , with the requirement for strict storage at low temperatures ( a so-called “ cold chain ”), use of needles for administration and a currently unknown ability to confer long-term protection in the face of emerging viral variants .
One completely unexplored alternative is the design and development of phage display-based vaccines , which represent an inexpensive and versatile tool for large-scale immunization . Bacteriophage ( phage ) are viruses that naturally only infect bacteria , and thus they are generally considered safe for use in humans . Phage particles are easy to genetically engineer or modify and produce in large quantities ; capable of stimulating both cellular and humoral immunity ;
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and are stable under harsh environmental conditions ( pH and temperature ).
In this study , the authors developed two independent phage display-based vaccination approaches against SARS-CoV-2 , the virus that causes COVID‐19 . The first is a peptide-directed phage particle that can be administered in an aerosolized form by inhalation . It is engineered with an epitope from the SARS-CoV-2 spike ( S ) protein together with a small ligand peptide to ensure it crossed from the lungs into the systemic circulation , where it produced a strong antibody response in mice . In the second approach , they engineered chimeric adeno-associated virus-phage ( AAVP ) particles to deliver the gene encoding for the entire S protein , which also stimulated a systemic and specific antibody response in mice .
This dual proof-of-concept experimentation demonstrates that phage display-based vaccine approaches are versatile platforms that could be used for rapid production of COVID‐19 vaccines that are cost-effective , needle-free , and can be safely stored long-term at room temperature . Combined with a theoretical structural biology approach to identify effective epitopes , this work provides a new framework for vaccine development . Further research and development of prototype COVID‐19 investigational vaccines and alternative methods of application such as inhalation are ongoing .
“ In the development of new vaccination strategies , the structure and strength of the local healthcare system is a key consideration ,” explains the study ’ s senior author Renata Pasqualini , Ph . D ., resident member of Rutgers Cancer Institute and professor and founding chief of the Division of Cancer Biology , Department of Radiation
Phage display-based vaccines represent an inexpensive and versatile tool for large-scale immunization .
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Study Directors Renata Pasqualini , Ph . D ., and Wadih Arap , M . D ., Ph . D .
Oncology at Rutgers NJMS . “ As such , the global COVID‐19 pandemic has raised awareness of public health inequity and the need for a rapid and accessible immunization process . In this context , the favorable biological attributes of phage particles might represent a potentially practical yet affordable alternative .”
The study ’ s other senior author , Wadih Arap , M . D ., Ph . D ., director of Rutgers Cancer Institute at University Hospital Newark and professor and chief of the Division of Hematology / Oncology , Department of Medicine , Rutgers NJMS , notes , “ Bacteriophage-based therapy has a long and rich history in medicine because native phage particles are not infectious to human cells . The new appeal here is that we were able to modify the phage particles so that they may now target cell surface receptors ; moreover , another potential application of this platform technology is the possibility of an inhaled vaccine administration .”
“ One of the challenges in designing these vaccines is that , when we insert the different SARS- CoV-2 spike epitopes into the phage particles , the structure of these peptides needs to stay intact as in the original protein ,” adds José N . Onuchic , Ph . D ., Harry C . and Olga K . Wiess Chair of Physics and professor of chemistry and biosciences at Rice University , who is a corresponding author on the study with Drs . Arap and Pasqualini . “ In this collaboration , we demonstrated that the epitopes that show the smallest deviations from the original structure are the ones most effective in creating immune protection , This initial success allows us to create a synergistic theoretical / experimental framework to discover new possible epitopes to improve these vaccines not only for SARS-CoV-2 but for other diseases as well .”