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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

ABSTRACT: Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as "boosts" against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

SUBMITTER: Kapingidza AB

PROVIDER: S-EPMC10689493 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Kapingidza A Brenda AB Marston Daniel J DJ Harris Caitlin C Wrapp Daniel D Winters Kaitlyn K Mielke Dieter D Xiaozhi Lu L Yin Qi Q Foulger Andrew A Parks Rob R Barr Maggie M Newman Amanda A Schäfer Alexandra A Eaton Amanda A Flores Justine Mae JM Harner Austin A Catanzaro Nicholas J NJ Mallory Michael L ML Mattocks Melissa D MD Beverly Christopher C Rhodes Brianna B Mansouri Katayoun K Van Itallie Elizabeth E Vure Pranay P Dunn Brooke B Keyes Taylor T Stanfield-Oakley Sherry S Woods Christopher W CW Petzold Elizabeth A EA Walter Emmanuel B EB Wiehe Kevin K Edwards Robert J RJ Montefiori David C DC Ferrari Guido G Baric Ralph R Cain Derek W DW Saunders Kevin O KO Haynes Barton F BF Azoitei Mihai L ML

Nature communications 20231130 1

Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent vi ...[more]

PMID: 38036525

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Project description:UnlabelledBackgroundNeuronal antibodies that show immunoreactivity across a broad range of species are important tools for comparative neuroanatomy. Nonetheless, the current antibody repertoire for non-model invertebrates is limited. Currently, only antibodies against the neuropeptide RFamide and the monoamine transmitter serotonin are extensively used. These antibodies label respective neuron-populations and their axons and dendrites in a large number of species across various animal phyla.ResultsSeveral other neuropeptides also have a broad phyletic distribution among invertebrates, including DLamides, FVamides, FLamides, GWamides and RYamides. These neuropeptides show strong conservation of the two carboxy-terminal amino acids and are α-amidated at their C-termini. We generated and affinity-purified specific polyclonal antibodies against each of these conserved amidated dipeptide motifs. We thoroughly tested antibody reactivity and specificity both by peptide pre-incubation experiments and by showing a close correlation between the immunostaining signals and mRNA expression patterns of the respective precursor genes in the annelid Platynereis. We also demonstrated the usefulness of these antibodies by performing immunostainings on a broad range of invertebrate species, including cnidarians, annelids, molluscs, a bryozoan, and a crustacean. In all species, the antibodies label distinct neuronal populations and their axonal projections. In the ciliated larvae of cnidarians, annelids, molluscs and bryozoans, a subset of antibodies reveal peptidergic innervation of locomotor cilia.ConclusionsWe developed five specific cross-species-reactive antibodies recognizing conserved two-amino-acid amidated neuropeptide epitopes. These antibodies allow specific labelling of peptidergic neurons and their projections in a broad range of invertebrates. Our comparative survey across several marine phyla demonstrates a broad occurrence of peptidergic innervation of larval ciliary bands, suggesting a general role of these neuropeptides in the regulation of ciliary swimming.

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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

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Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

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