Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

Powell, Abigail E.; Xu, Duo; Roth, Gillie A.; Zhang, Kaiming; Chiu, Wah; Appel, Eric A.; Kim, Peter S.

doi:10.3389/fimmu.2022.942897

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

Journal Article · Wed Aug 24 00:00:00 EDT 2022 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2022.942897· OSTI ID:2471720

Powell, Abigail E. ^[1]; Xu, Duo ^[1]; Roth, Gillie A. ^[1]; Zhang, Kaiming ^[1]; Chiu, Wah ^[2]; Appel, Eric A. ^[1]; Kim, Peter S. ^[3]

Stanford University, CA (United States)
Stanford University, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States) ; SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Stanford University, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Ebola virus (EBOV), a member of the Filoviridae family of viruses and a causative agent of Ebola Virus Disease (EVD), is a highly pathogenic virus that has caused over twenty outbreaks in Central and West Africa since its formal discovery in 1976. The only FDA-licensed vaccine against Ebola virus, rVSV-ZEBOV-GP (Ervebo®), is efficacious against infection following just one dose. However, since this vaccine contains a replicating virus, it requires ultra-low temperature storage which imparts considerable logistical challenges for distribution and access. Additional vaccine candidates could provide expanded protection to mitigate current and future outbreaks. Here, we designed and characterized two multimeric protein nanoparticle subunit vaccines displaying 8 or 20 copies of GPΔmucin, a truncated form of the EBOV surface protein GP. Single-dose immunization of mice with GPΔmucin nanoparticles revealed that neutralizing antibody levels were roughly equivalent to those observed in mice immunized with non-multimerized GPΔmucin trimers. These results suggest that some protein subunit antigens do not elicit enhanced antibody responses when displayed on multivalent scaffolds and can inform next-generation design of stable Ebola virus vaccine candidates.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2471720

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 13; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
GPDmucin
Immunology
ebolavirus
glycoprotein
protein nanoparticles
subunit vaccine

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

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