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SARS-CoV-2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
Yao Ma1, Ye Wang1, Chunhong Dong1
1Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30302, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|May 24, 2022
Summary
Investigating SARS-CoV-2 spike protein subunits revealed that the S2 subunit induces potent antibody-dependent cellular cytotoxicity (ADCC), while prefusion spike protein (Pre) offers stronger neutralization. Nanoparticles combining both S2 and Pre enhance both responses for broader vaccine potential.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a significant global health challenge.
- Current vaccines using prefusion spike protein (Pre) show limitations in protecting against diverse SARS-CoV-2 variants.
- The conserved S2 subunit of the spike protein presents an alternative target for broader immune responses.
Purpose of the Study:
- To compare the immunogenicity of the SARS-CoV-2 spike protein S2 subunit versus the prefusion spike protein (Pre).
- To evaluate the potential of incorporating S2 and Pre into double-layered protein nanoparticles for enhanced vaccine efficacy.
- To assess the breadth and durability of immune responses induced by nanoparticle-based vaccines.
Main Methods:
- Vesicular stomatitis virus pseudovirus-based neutralization assays.
- Assessment of antibody-dependent cellular cytotoxicity (ADCC) activity.
- Immunization studies using soluble proteins and double-layered protein nanoparticles (Pre/S2).
- Analysis of immunoglobulin G (IgG) antibody responses and their longevity.
Main Results:
- Prefusion spike protein (Pre) elicited robust neutralization but lower ADCC compared to the S2 subunit.
- The S2 subunit induced potent ADCC activity with broader, albeit weaker, neutralization.
- Double-layered protein nanoparticles incorporating both S2 and Pre (Pre/S2) enhanced both neutralizing antibodies and ADCC activity.
- Nanoparticle immunization resulted in more potent and sustained (≥4 months) balanced IgG antibody responses compared to soluble protein mixtures.
Conclusions:
- Double-layered protein nanoparticles effectively enhance both neutralizing and ADCC immune responses against SARS-CoV-2.
- The Pre/S2 nanoparticle vaccine strategy shows potential for developing broader and more effective SARS-CoV-2 vaccines.
- This approach may offer improved protection against current and emerging SARS-CoV-2 variants with favorable safety profiles.
