Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer

Baric, R.S.

Brown, B.

Carter, L.

Chalk, S.

Chen, C.

Chow, C.M.

Chu, H.Y.

Dinnon, III, K.H.

Fiala, B.

Fuller, D.H.

Fuller, J.T.

Gralinski, L.E.

Guerriero, K.

Gully, K.L.

Guttman, M.

Hodge, E.A.

Kellam, P.

Kepl, E.

King, N.P.

Kraft, J.C.

Lee, E.-C.

Lee, K.K.

Leist, S.R.

Lewis, T.B.

Miranda, M.C.

Murphy, M.

Navarro, M.J.

O&apos

Ogohara, C.

Palser, A.

Pepper, M.

Pettie, D.

Pham, M.N.

Ravichandran, R.

Schäfer, A.

Sheahan, T.P.

Shehata, L.

Sydeman, C.

Tse, L.V.

Veesler, D.

Walls, A.C.

Wrenn, S.

Cell

A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic

Walls, AC

Fiala, B

Schäfer, A

Wrenn, S

Pham, MN

Murphy, M

Tse, LV

Shehata, L

O'Connor, MA

Chen, C

Navarro, MJ

Miranda, MC

Pettie, D

Ravichandran, R

Kraft, JC

Ogohara, C

Palser, A

Chalk, S

Lee, E-C

Guerriero, K

Kepl, E

Chow, CM

Sydeman, C

Hodge, EA

Brown, B

Fuller, JT

Dinnon, KH

Gralinski, LE

Leist, SR

Gully, KL

Lewis, TB

Guttman, M

Chu, HY

Lee, KK

Fuller, DH

Baric, RS

Kellam, P

Carter, L

Pepper, M

Sheahan, TP

Veesler, D

King, NP

Spiral - Imperial College Digital Repository

English

Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2

Carolina Digital Repository

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

https://cdr.lib.unc.edu/downloads/1j92gh03p

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2

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