Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens

John C. Kraft, Minh N. Pham, Laila Shehata, Mitch Brinkkemper, Seyhan Boyoglu-Barnum, Kaitlin R. Sprouse, Alexandra C. Walls, Suna Cheng, Mike Murphy, Deleah Pettie, Maggie Ahlrichs, Claire Sydeman, Max Johnson, Alyssa Blackstone, Daniel Ellis, Rashmi Ravichandran, Brooke Fiala, Samuel Wrenn, Marcos Miranda, Kwinten SliepenPhilip J. M. Brouwer, Aleksandar Antanasijevic, David Veesler, Andrew B. Ward, Masaru Kanekiyo, Marion Pepper, Rogier W. Sanders, Neil P. King

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15 Citations (Scopus)


Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.
Original languageEnglish
Article number100780
JournalCell Reports Medicine
Issue number10
Publication statusPublished - 18 Oct 2022

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