ArticleProceedings of the National Academy of Sciences of the United States of America2019
Protect, modify, deprotect (PMD): A strategy for creating vaccines to elicit antibodies targeting a specific epitope.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 49 citations in OpenAlex.
- Design of Epitope-Focused Vaccines via Epitope Cleavage.ACS central science · 2026Article
- A self-assembled protein nanocage as a universal influenza vaccine induces enhanced broadly cross-reactive immunity.Biomaterials · 2026Article
- MAAD: multidimensional antiviral antibody database.Protein & cell · 2026Article
- Engineered PCV2 VLPs for Antigen Delivery: A Platform for Next-Generation Veterinary Vaccines.Transboundary and emerging diseases · 2026Review
- Manipulation of immunodominant variable epitopes of norovirus capsid protein elicited cross-blocking antibodies to different GII.4 variants despite the low potency of the polyclonal sera.Journal of virology · 2025Article
- Sustained Vaccine Exposure Elicits More Rapid, Consistent, and Broad Humoral Immune Responses to Multivalent Influenza Vaccines.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Influenza A virus rapidly adapts particle shape to environmental pressures.Nature microbiology · 2025Article
- Article
- DNA and protein-generated chimeric molecules for delivery of influenza viral epitopes in mouse and humanized NSG transfer models.Human vaccines & immunotherapeutics · 2024Review
- Engineering a SARS-CoV-2 Vaccine Targeting the Receptor-Binding Domain Cryptic-Face via Immunofocusing.ACS central science · 2024Article
- An Engineered N-Glycosylated Dengue Envelope Protein Domain III Facilitates Epitope-Directed Selection of Potently Neutralizing and Minimally Enhancing Antibodies.ACS infectious diseases · 2024Article
- Vaccine design via antigen reorientation.Nature chemical biology · 2024Article
- Engineering a SARS-CoV-2 vaccine targeting the RBD cryptic-face via immunofocusing.bioRxiv : the preprint server for biology · 2024Article
- Goldilocks Zone of Preexisting Immunity: Too Little or Too Much Suppresses Diverse Antibody Responses Against Influenza Viruses.The Journal of infectious diseases · 2024Article
- Bringing immunofocusing into focus.NPJ vaccines · 2024Review
- Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.Cell reports · 2023Article
- Precise modification of the surface charge of antigen enhances vaccine immunogenicity.Innovation (Cambridge (Mass.)) · 2023Article
- Combinatorial immune refocusing within the influenza hemagglutinin head elicits cross-neutralizing antibody responses.bioRxiv : the preprint server for biology · 2023Article
- Simplified Purification of Glycoprotein-Modified Ferritin Nanoparticles for Vaccine Development.Biochemistry · 2023Article
- Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors.Nature chemical biology · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In creating vaccines against infectious agents, there is often a desire to direct an immune response toward a particular conformational epitope on an antigen. We present a method, called protect, modify, deprotect (PMD), to generate immunogenic proteins aimed to direct a vaccine-induced antibody (Ab) response toward an epitope defined by a specific monoclonal Ab (mAb). The mAb is used to protect the target epitope on the protein. Then the remaining exposed surfaces of the protein are modified to render them nonimmunogenic. Finally, the epitope is deprotected by removal of the mAb. The resultant protein is modified at surfaces other than the target epitope. We validate PMD using a well-characterized antigen, hen egg white lysozyme, then demonstrate the utility of PMD using influenza virus hemagglutinin (HA). We use an mAb to protect a highly conserved epitope on the stem domain of HA. Exposed surface amines are then modified with short polyethylene glycol chains. The resultant antigen shows markedly reduced binding to mAbs that target the head region of HA, while maintaining binding to mAbs at the epitope of interest. This antigenic preference is also observed with yeast cells displaying Ab fragments. Antisera from guinea pigs immunized with the PMD-modified HA show increased cross-reactivity with HAs from other influenza strains, compared with antisera obtained with unmodified HA trimers. PMD has the potential to direct an Ab response at high resolution and could be used in combination with other such strategies. There are many attractive targets for the application of PMD.
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