RT Journal Article
SR Electronic
T1 SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.09.443331
DO 10.1101/2021.05.09.443331
A1 M. Gordon Joyce
A1 Wei-Hung Chen
A1 Rajeshwer S. Sankhala
A1 Agnes Hajduczki
A1 Paul V. Thomas
A1 Misook Choe
A1 William Chang
A1 Caroline E. Peterson
A1 Elizabeth Martinez
A1 Elaine B. Morrison
A1 Clayton Smith
A1 Aslaa Ahmed
A1 Lindsay Wieczorek
A1 Alexander Anderson
A1 Rita E. Chen
A1 James Brett Case
A1 Yifan Li
A1 Therese Oertel
A1 Lorean Rosado
A1 Akshaya Ganesh
A1 Connor Whalen
A1 Joshua M. Carmen
A1 Letzibeth Mendez-Rivera
A1 Christopher Karch
A1 Neelakshi Gohain
A1 Zuzana Villar
A1 David McCurdy
A1 Zoltan Beck
A1 Jiae Kim
A1 Shikha Shrivastava
A1 Ousman Jobe
A1 Vincent Dussupt
A1 Sebastian Molnar
A1 Ursula Tran
A1 Chandrika B. Kannadka
A1 Michelle Zemil
A1 Htet Khanh
A1 Weimin Wu
A1 Matthew A. Cole
A1 Debra K. Duso
A1 Larry W. Kummer
A1 Tricia J. Lang
A1 Shania E. Muncil
A1 Jeffrey R. Currier
A1 Shelly J. Krebs
A1 Victoria R. Polonis
A1 Saravanan Rajan
A1 Patrick M. McTamney
A1 Mark T. Esser
A1 William W. Reiley
A1 Morgane Rolland
A1 Natalia de Val
A1 Michael S. Diamond
A1 Gregory D. Gromowski
A1 Gary R. Matyas
A1 Mangala Rao
A1 Nelson L. Michael
A1 Kayvon Modjarrad
YR 2021
UL http://biorxiv.org/content/early/2021/05/10/2021.05.09.443331.abstract
AB The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.HIGHLIGHTSIterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challengeCompeting Interest StatementM.G.J. and K.M. are named as inventors on International Patent Application No. WO/2021/21405 entitled Vaccines against SARS-CoV-2 and other coronaviruses. M.G.J. is named as an inventor on International Patent Application No. WO/2018/081318 and U.S. patent 10,960,070 entitled Prefusion Coronavirus Spike Proteins and Their Use. Z.B. is named as an inventor on U.S. patent 10,434,167 entitled Non-toxic adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition and a saponin. Z.B. and G.R.M are named inventors on Compositions And Methods For Vaccine Delivery, US Patent Application: 16/607,917. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals and Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received funding support in sponsored research agreements from Moderna, Vir Biotechnology and Emergent BioSolutions. S.R., P.M.M., and M.T.E. are employees of AstraZeneca and currently hold AstraZeneca stock or stock options. Zoltan Beck is currently employed at Pfizer.