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The Design of Vaccines Based on the Shielding of Antigenic Site Ø of a Respiratory Syncytial Virus Fusion Protein Immunogen
Author(s) -
Frey Steven J.,
Varner Chad,
Arsiwala Ammar,
Currier Michael G.,
Moore Martin L.,
Kane Ravi S.
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202000714
Subject(s) - immunogen , virology , immune system , neutralizing antibody , antigen , virus , antibody , biology , fusion protein , immunology , monoclonal antibody , recombinant dna , biochemistry , gene
Respiratory syncytial virus (RSV), for which there is currently no licensed vaccine, displays a fusion (F) protein that is considered a vaccine target. This protein has an antigenic site called site Ø, which has been shown to elicit potent, neutralizing antibodies and has therefore been considered important in the formulation of RSV vaccines. However, this site is also the least conserved region on the F protein across RSV subtypes. Therefore, directing the immune response away from site Ø and refocusing it toward more conserved parts of the RSV F protein might serve to better elicit broadly neutralizing antibodies. To demonstrate that directing the immune response away from site Ø is a viable approach, a prefusion F‐based vaccine based on an F protein with a shielded site Ø is generated. Sera from mice immunized with multivalent scaffolds presenting this immunogen is capable of neutralizing RSV of both subtypes. This result may have application in the development of an effective and broadly protective RSV vaccine.