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Principal Investigator: Joel H Collier
Organization: DUKE UNIVERSITY
Fiscal Year: 2021
Award: $435,384
Funding agency: National Institute of Allergy and Infectious Diseases
Even when vaccines are rapidly developed and shown to be efficacious and safe, vaccination
campaigns continue to be hampered by public hesitancy and by challenges distributing vaccines equitably
around the globe. Vaccine hesitancy, where individuals refuse or delay vaccination, has been a persistent
challenge, affecting a third to a quarter of individuals in the US and globally. Inequitably, it affects racial and
ethnic minority communities particularly strongly, and in 2019 the World Health Organization named vaccine
hesitancy as one of the top-ten threats to global health. Needle-based injections, which increase vaccine
reactogenicity, are a significant driver of vaccine hesitancy. A second fundamental hurdle in equitable
availability of vaccines involves the chain of distribution. Most vaccines must be transported and stored within
a continuous cold-chain to prevent loss of potency, making global distribution challenging. In the face of these
limitations, lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across
weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking
vaccines, yet the issues of global distribution and patient acceptance are exponentially more challenging with
repeated dosing. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered
specifically for the sublingual route to provide for effective vaccination. The project aims to design a shelf-
stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based
vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide
platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing
and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of-
concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with
Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of
immune responses remain to be articulated. Therefore the objective of the project is to articulate these design
rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size,
charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and
cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza,
zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in
mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and
the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from
Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).
Terms: <0-11 years old><Adhesives><Adjuvant><Affect><Allergic><Antibody Response><Antigenic Determinants><Antigens><Attention><Autoimmune Diseases><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Determinants><Biocompatible Materials><Biomaterials><Biomedical Engineering><Buccal Mucosa><Cancers><Cell Body><Cells><Charge><Child><Child Youth><Children (0-21)><Cold Chains><Communicable Diseases><Complex><Disease><Disorder><Distress><Domestic Rabbit><Dose><Engineering><Epitopes><Experimental Designs><Face><Glycoproteins><Grippe><HIV-1><HIV-I><HIV1><Human><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Immune mediated therapy><Immune response><Immunization><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunological response><Immunologically Directed Therapy><Immunologist><Immunostimulation><Immunotherapeutic agent><Immunotherapy><Individual><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammatory><Influenza><Injections><Institutes><Investigation><Logistics><Lymphatic><Lymphatic Tissue><Lymphoid Tissue><Malignant Neoplasms><Malignant Tumor><Mice><Mice Mammals><Modeling><Modern Man><Modification><Molecular><Mouth Mucosa><Mucins><Mucosa><Mucosal Tissue><Mucous Membrane><Mucus Glycoprotein><Murine><Mus><Names><Needles><Oral Mucosa><Oral mucous membrane structure><Oryctolagus cuniculus><Pain><Pain-Free><Painful><Patients><Penetration><Peptides><Polymers><Protein Fragment><Proteins><Public Health><RNA vaccine><RNA-based vaccine><Rabbits><Rabbits Mammals><Refrigeration><Regimen><Route><STING agonists><Schools><Shapes><Specialist><Surface><System><T-Cell Epitopes><T-Lymphocyte Epitopes><Tablets><Technology><Temperature><Tongue><Vaccination><Vaccines><Work><World Health Organization><ZIKA><access to vaccination><access to vaccines><autoimmune condition><autoimmune disorder><base><bio-engineered><bio-engineers><bioengineering><biological material><deploy vaccines><design><designing><distribute vaccines><engineered immune system><ethnic minority><ethnic minority population><experiment><experimental research><experimental study><faces><facial><global health><hesitant to vaccination><host response><immune drugs><immune engineering><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapeutics><immune-based therapies><immune-based treatments><immuno therapy><immunoengineering><immunogen><immunogenic><immunologic preparation><immunologic therapeutics><immunoresponse><immunotherapeutics><immunotherapy agent><improved><innovate><innovation><innovative><interest><mRNA vaccine><mRNA-based vaccine><malignancy><minority communities><molecular assembly><molecular assembly/self assembly><molecular self assembly><mouse model><murine model><nano fiber><nanofiber><nanofibrous><neoplasm/cancer><new vaccines><next generation vaccines><novel vaccines><oral mucosae><oral mucosal><peptide immunization><peptide vaccination><physical property><prevent><preventing><racial minority><response><self assembly><success><trafficking><vaccination access><vaccination availability><vaccination hesitancy><vaccination strategy><vaccine access><vaccine availability><vaccine deployment><vaccine distribution><vaccine hesitancy><vaccine hesitant><vaccine roll-out><vaccine rollout><youngster>