Bringing immunofocusing into focus

Abstract

Immunofocusing is a strategy to create immunogens that redirect humoral immune responses towards a targeted epitope and away from non-desirable epitopes. Immunofocusing methods often aim to develop “universal” vaccines that provide broad protection against highly variant viruses such as influenza virus, human immunodeficiency virus (HIV-1), and most recently, severe acute respiratory syndrome coronavirus (SARS-CoV-2). We use existing examples to illustrate five main immunofocusing strategies—cross-strain boosting, mosaic display, protein dissection, epitope scaffolding, and epitope masking. We also discuss obstacles for immunofocusing like immune imprinting. A thorough understanding, advancement, and application of the methods we outline here will enable the design of high-resolution vaccines that protect against future viral outbreaks.

An Engineered N-Glycosylated Dengue Envelope Protein Domain III Facilitates Epitope-Directed Selection of Potently Neutralizing and Minimally Enhancing Antibodies

“…A glycan-masking strategy utilizes N-glycans as shields to prevent antibody binding to specific epitopes on a given antigen protein. , The strategy has been successfully utilized to control antibody recognition across multiple antigens. For example, a glycan-masked version of an HIV vaccine candidate eOD-GT8 was able to focus the antibody response to the targeted CD4-binding site .…”

Heterologous Prime-Boost with Immunologically Orthogonal Protein Nanoparticles for Peptide Immunofocusing

“…One strategy to avert primary addiction is heterologous prime-boost vaccination, in which the same peptide epitope is presented to immune cells on different protein scaffolds over the course of the immunization schedule. − Ideally, the proliferation of B cells directed against the vaccine scaffolds is thereby minimized while the immune response directed against the common peptide epitope is concurrently maximized. Here, we attempted to focus immune responses against a 20-mer SARS-CoV-2 peptide by combining our engineered encapsulin scaffolds with a previously reported variant of the PP7 RNA phage VLP in several heterologous prime-boost regimens.…”

“…43−45 Ideally, the proliferation of B cells directed against the vaccine scaffolds is thereby minimized while the immune response directed against the common peptide epitope is concurrently maximized. Here, we attempted to focus immune responses 46 against a 20-mer SARS-CoV-2 peptide by combining our engineered encapsulin scaffolds with a previously reported variant of the PP7 RNA phage VLP in several heterologous prime-boost regimens.…”