Next-generation nanovaccine induces durable immunity and protects against SARS-CoV-2.

Publication date: Jul 15, 2024

While first generation SARS-CoV-2 vaccines were effective in slowing the spread and severity of disease during the COVID-19 pandemic, there is a need for vaccines capable of inducing durable and broad immunity against emerging variants of concern. Nanoparticle-based vaccines (i. e., “nanovaccines”) composed of polyanhydride nanoparticles and pentablock copolymer micelles have previously been shown to protect against respiratory pathogens, including influenza A virus, respiratory syncytial virus, and Yersinia pestis. In this work, a nanovaccine containing SARS-CoV-2 spike and nucleocapsid antigens was designed and optimized. The optimized nanovaccine induced long-lived systemic IgG antibody responses against wild-type SARS-CoV-2 virus. In addition, the nanovaccine induced antibody responses capable of neutralization and cross-reactivity to multiple SARS-CoV-2 variants (including B. 1.1. 529) and antigen-specific CD4 and CD8 T cell responses. Finally, the nanovaccine protected mice against a lethal SARS-CoV-2 challenge, setting the stage for advancing particle-based SARS-CoV-2 nanovaccines. STATEMENT OF SIGNIFICANCE: First-generation SARS-CoV-2 vaccines were effective in slowing the spread and limiting the severity of COVID-19. However, current vaccines target only one antigen of the virus (i. e., spike protein) and focus on the generation of neutralizing antibodies, which may be less effective against new, circulating strains. In this work, we demonstrated the ability of a novel nanovaccine platform, based on polyanhydride nanoparticles and pentablock copolymer micelles, to generate durable and broad immunity against SARS-CoV-2. These nanovaccines induced long-lasting (> 62 weeks) serum antibody responses which neutralized binding to ACE2 receptors and were cross-reactive to multiple SARS-CoV-2 variants. Additionally, mice immunized with the SARS-CoV-2 nanovaccine showed a significant increase of antigen-specific T cell responses in the draining lymph nodes and spleens. Together, these nanovaccine-induced immune responses contributed to the protection of mice against a lethal challenge of live SARS-CoV-2 virus, indicating that this nanovaccine platform is a promising next-generation SARS-CoV-2 vaccine.

Concepts Keywords
Cd4 Animals
Micelles Antibodies, Neutralizing
Nanoparticle Antibodies, Neutralizing
Optimized Antibodies, Viral
Vaccines Antibodies, Viral
Antigen-specific T cell
CD8-Positive T-Lymphocytes
COVID-19
COVID-19 Vaccines
COVID-19 Vaccines
Female
Humans
Mice
Micelles
Micelles
Nanoparticles
Nanovaccine
Nanovaccines
Nanovaccines
Neutralizing antibody
Polyanhydrides
Polyanhydrides
SARS-CoV-2
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Semantics

Type Source Name
disease VO effective
disease MESH COVID-19 pandemic
drug DRUGBANK Influenza A virus
disease VO Respiratory syncytial virus
disease IDO cell
disease VO immunized
disease VO vaccine
disease VO Glycoprotein

Original Article

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