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Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection.

ABSTRACT: Recent outbreaks of emerging infectious diseases, such as Ebola virus disease (EVD), highlight the urgent need to develop effective countermeasures, including prophylactic vaccines. Subunit proteins derived from pathogens provide a safe source of antigens for vaccination, but they are often limited by their low immunogenicity. We have developed a multilamellar vaccine particle (MVP) system composed of lipid-hyaluronic acid multi-cross-linked hybrid nanoparticles for vaccination with protein antigens and demonstrate their efficacy against Ebola virus (EBOV) exposure. MVPs efficiently accumulated in dendritic cells and promote antigen processing. Mice immunized with MVPs elicited robust and long-lasting antigen-specific CD8+ and CD4+ T cell immune responses as well as humoral immunity. A single-dose vaccination with MVPs delivering EBOV glycoprotein achieved an 80% protection rate against lethal EBOV infection. These results suggest that MVPs offer a promising platform for improving recombinant protein-based vaccine approaches.

SUBMITTER: Fan Y

PROVIDER: S-EPMC6834342 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection.

Fan Yuchen Y Stronsky Sabrina M SM Xu Yao Y Steffens Jesse T JT van Tongeren Sean A SA Erwin Amanda A Cooper Christopher L CL Moon James J JJ

ACS nano 20190912 10

Recent outbreaks of emerging infectious diseases, such as Ebola virus disease (EVD), highlight the urgent need to develop effective countermeasures, including prophylactic vaccines. Subunit proteins derived from pathogens provide a safe source of antigens for vaccination, but they are often limited by their low immunogenicity. We have developed a multilamellar vaccine particle (MVP) system composed of lipid-hyaluronic acid multi-cross-linked hybrid nanoparticles for vaccination with protein anti ...[more]

PMID: 31497947

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Project description:Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein, was loaded in CaCO3 microspheres, which were further coated with tannic acid (TA)/polyethylene glycol (PEG) LBL films. The single-injection vaccine was obtained by mixing the microspheres coated with different thickness of TA/PEG films. Because of the unique constant-rate erosion behavior of the TA/PEG coatings, this system allows for distinct multiple pulsatile release of antigen, closely mimicking the release profile of antigen in conventional multiple dose vaccines. Immunization with the single injection vaccine induces potent and persistent S1-specific humoral and cellular immune responses in mice. The sera from the vaccinated animal exhibit robust in vitro viral neutralization ability. More importantly, the immune response and viral inhibition induced by the single injection vaccine are as strong as that induced by the corresponding multiple dose vaccine, because they share the same antigen release profile. STATEMENT OF SIGNIFICANCE: Vaccines are the most powerful and cost-effective weapons against infectious diseases such as COVID-19. However, current vaccination schedules, including the COVID-19 vaccines, require multiple doses to be administered. Herein a single-injection COVID-19 vaccine is designed using a highly programmable release system. This vaccine releases antigens in a pulsatile manner, closely mimicking the release pattern of antigens in conventional multiple dose vaccines. As a result, one single injection of the new vaccine induces an immune response and viral inhibition similar to that induced by the corresponding multiple-dose vaccine approach.

Dataset Information

Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection.

Publications

Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection.

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