RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge
Name
wong-et-al-2022-rbd-vlp-vaccines-adjuvanted-with-alum-or-swe-protect-k18-hace2-mice-against-sars-cov-2-voc-challenge.pdf
Description
Published version
Size
2.72 MB
Format
Adobe PDF
Checksum (MD5)
5a21eaa1b66e5c44746938466030e9c7
Author(s)
Wong, Ting Y
Russ, Brynnan P
Lee, Katherine S
Miller, Olivia A
Kang, Jason
Cooper, Melissa
Winters, Michael T
Rodriguez-Aponte, Sergio A
Dalvie, Neil C
Johnston, Ryan S
Date Issued
August 15, 2022
Journal
mSphere
Publisher
American Society for Microbiology
Citation
Wong TY,Russ BP,Lee KS,Miller OA,Kang J,Cooper M,Winters MT, Rodriguez-Aponte SA,Dalvie NC,Johnston RS, Rader NA,Wong ZY,Cyphert HA, Martinez I,,Shaligram U, Batwal S, Lothe R, Chandrasekaran R, Nagar G, Rajurkar M, Rao H, Bevere JR,Barbier M,Love JC, Damron FH, 2022. RBD-VLP Vaccines Adjuvanted with Alum or SWE Protect K18-hACE2 Mice against SARS-CoV-2 VOC Challenge. mSphere 7:e00243-22.
Version
Final published version
Abstract
The ongoing COVID-19 pandemic has contributed largely to the global
vaccine disparity. Development of protein subunit vaccines can help alleviate shortages of COVID-19 vaccines delivered to low-income countries. Here, we evaluated
the efficacy of a three-dose virus-like particle (VLP) vaccine composed of hepatitis B
surface antigen (HBsAg) decorated with the receptor binding domain (RBD) from the
Wuhan or Beta SARS-CoV-2 strain adjuvanted with either aluminum hydroxide (alum)
or squalene in water emulsion (SWE). RBD HBsAg vaccines were compared to the
standard two doses of Pfizer mRNA vaccine. Alum-adjuvanted vaccines were composed of either HBsAg conjugated with Beta RBD alone (b RBD HBsAg1Al) or a combination of both Beta RBD HBsAg and Wuhan RBD HBsAg (b/Wu RBD HBsAg1Al).
RBD vaccines adjuvanted with SWE were formulated with Beta RBD HBsAg (b RBD
HBsAg1SWE) or without HBsAg (b RBD1SWE). Both alum-adjuvanted RBD HBsAg vaccines generated functional RBD IgG against multiple SARS-CoV-2 variants of concern
(VOC), decreased viral RNA burden, and lowered inflammation in the lung against
Alpha or Beta challenge in K18-hACE2 mice. However, only b/Wu RBD HBsAg1Al was
able to afford 100% survival to mice challenged with Alpha or Beta VOC. Furthermore,
mice immunized with b RBD HBsAg1SWE induced cross-reactive neutralizing antibodies
against major VOC of SARS-CoV-2, lowered viral RNA burden in the lung and brain, and
protected mice from Alpha or Beta challenge similarly to mice immunized with Pfizer
mRNA. However, RBD1SWE immunization failed to protect mice from VOC challenge.
Our findings demonstrate that RBD HBsAg VLP vaccines provided similar protection profiles to the approved Pfizer mRNA vaccines used worldwide and may offer protection
against SARS-CoV-2 VOC.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1128/msphere.00243-22
