Document text
Principal Investigator: Szu-Wen Wang
Organization: UNIVERSITY OF CALIFORNIA-IRVINE
Fiscal Year: 2024
Award: $196,250
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY / ABSTRACT
Vaccines have been very effective at protecting against infectious diseases that pose
serious threats to human health. However, prophylactic vaccines can also be limited, particularly
if antigenic drift occurs to create variants of the pathogen; this can result in vaccines losing
potency over time, needing boosters to confer protection, and lower neutralization efficacy on
emerging viral variants – consequences which are observed in the current COVID-19 pandemic.
Recent studies have shown that the release kinetics of vaccines can be important in establishing
lasting and efficacious immunity. In particular, extending the exposure to antigens can result in
higher antibody titers and increased diversity of neutralizing antibodies that target a more diverse
set of epitopes, relative to immune responses from conventional bolus vaccination. Furthermore,
vaccines made from protein-based nanoparticles can elicit increased antibody production,
broader antigen cross-reactivity, and a more balanced Th1/Th2 response. This study tests the
hypothesis that the synergy in combining the effects of nanoparticle vaccines for effective antigen
presentation, together with a slower release to give a longer exposure to the vaccine, will elicit
increased durability of the immune response and a broader cross-reactivity for emerging viral
variants.
To test this hypothesis, we propose to encapsulate protein nanoparticle vaccines with a
biodegradable PLGA-PEG-PLGA (PPP)-based polymer to modulate the kinetics of its release
from an in vivo vaccine depot. This extended-release vaccine strategy will then be applied
towards SARS-CoV-2. We will evaluate the durability of the proposed vaccine strategy’s potency
and the breadth of cross-reactive immune responses toward the variants of SARS-CoV-2 and
other types of coronaviruses. Our specific aims are to: (1) create controlled-release nanoparticle
depot vaccines against SARS-CoV-2, and (2) determine the efficacy and immunological
responses to these vaccine nanoparticles that are encapsulated by the polymeric depot. Because
the design of these vaccines is modular and different antigens can be exchanged in a relatively
straightforward approach, the successful implementation of this proposed strategy for coronavirus
antigens could have broader applicability towards the development of vaccines for other infectious
pathogens.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Ab response><Adjuvant><Antibodies><Antibody Formation><Antibody Production><Antibody Response><Antibody titer measurement><Antigen Presentation><Antigenic Determinants><Antigens><Assay><Binding Determinants><Bioassay><Biological Assay><Blood Serum><Bolus><Bolus Infusion><Booster Immunization><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 vaccine><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 years><COVID19 virus><Cancers><Cell Body><Cells><CoV-2><CoV2><Communicable Diseases><Coronaviridae><Coronavirus><Encapsulated><Epitopes><Exposure to><Formulation><Grippe><Health><Histologic><Histologically><Human><Hydrogels><IVIS SpectrumCT><IVIS imaging><IVIS optical imaging><IVIS spectral imaging><IVIS spectrum><IVIS system><Immune><Immune response><Immunes><Immunity><Immunization><Immunological response><In Vitro><Individual><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Influenza><Injections><Kinetics><Libraries><Malignant Neoplasms><Malignant Tumor><Measures><Mediating><Mice><Mice Mammals><Modern Man><Murine><Mus><Nature><Physiologic><Physiological><Polymers><Preventative vaccine><Preventive vaccine><Prophylactic vaccine><Protein Array><Protein Engineering><Proteins><Receptor Protein><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccine><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Secondary Immunization><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Site><Surface><System><T cell response><T-Cells><T-Lymphocyte><Temperature><Testing><Time><Transition Temperature><Vaccination><Vaccine Design><Vaccines><Variant><Variation><Viral><Virus><Work><Wuhan coronavirus><antibody biosynthesis><antibody titering><biodegradable polymer><bioresorbable polymer><booster vaccination><controlled release><corona virus><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 vaccine><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cross reactivity><cytokine><degradable polymer><deliver vaccines><design><designing><determine efficacy><develop a vaccine><develop vaccines><development of a vaccine><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><emerging pathogen><evaluate efficacy><examine efficacy><genetic protein engineering><hCoV19><host response><immune response to vaccination><immune response to vaccines><immune system response><immunogen><immunoglobulin biosynthesis><immunoresponse><improved><in vivo><in vivo imaging system><malignancy><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><nano label><nano particle><nano vaccine><nano-sized particle><nanolabel><nanoparticle><nanosized particle><nanovaccine><neoplasm/cancer><neutralizing antibody><new pathogen><novel pathogen><pandemic><pandemic disease><particle><pathogen><polymer><polymeric><protein design><receptor><receptor binding><receptor bound><response><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><synergism><thymus derived lymphocyte><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine candidates against SARS-CoV-2><vaccine delivery><vaccine development><vaccine effectiveness><vaccine for novel coronavirus><vaccine formulation><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine strategy><vaccines preventing COVID><vaccines to prevent COVID>