Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Uri Elia; Shahar Rotem; Erez Bar-Haim; Srinivas Ramishetti; Gonna Somu Naidu; David Gur; Moshe Aftalion; Ma'ayan Israeli; Adi Bercovich-Kinori; Ron Alcalay; Efi Makdasi; Theodor Chitlaru; Ronit Rosenfeld; Tomer Israely; Sharon Melamed; Inbal Abutbul Ionita; Dganit Danino; Dan Peer; Ofer Cohen

doi:10.1021/acs.nanolett.1c01284

Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Uri Elia, Shahar Rotem, Erez Bar-Haim, Srinivas Ramishetti, Gonna Somu Naidu, David Gur, Moshe Aftalion, Ma'ayan Israeli, Adi Bercovich-Kinori, Ron Alcalay, Efi Makdasi, Theodor Chitlaru, Ronit Rosenfeld, Tomer Israely, Sharon Melamed, Inbal Abutbul Ionita, Dganit Danino, Dan Peer^*, Ofer Cohen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.

Original language	English
Pages (from-to)	4774-4779
Number of pages	6
Journal	Nano Letters
Volume	21
Issue number	11
DOIs	https://doi.org/10.1021/acs.nanolett.1c01284
State	Published - 9 Jun 2021

Funding

Funders	Funder number
Lewis Trust

Keywords

COVID-19
SARS-CoV-2
ionizable lipids
lipid nanoparticles
mRNA vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.nanolett.1c01284

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Elia, U., Rotem, S., Bar-Haim, E., Ramishetti, S., Naidu, G. S., Gur, D., Aftalion, M., Israeli, M., Bercovich-Kinori, A., Alcalay, R., Makdasi, E., Chitlaru, T., Rosenfeld, R., Israely, T., Melamed, S., Abutbul Ionita, I., Danino, D., Peer, D., & Cohen, O. (2021). Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection. Nano Letters, 21(11), 4774-4779. https://doi.org/10.1021/acs.nanolett.1c01284

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title = "Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection",

abstract = "The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.",

keywords = "COVID-19, SARS-CoV-2, ionizable lipids, lipid nanoparticles, mRNA vaccine",

author = "Uri Elia and Shahar Rotem and Erez Bar-Haim and Srinivas Ramishetti and Naidu, {Gonna Somu} and David Gur and Moshe Aftalion and Ma'ayan Israeli and Adi Bercovich-Kinori and Ron Alcalay and Efi Makdasi and Theodor Chitlaru and Ronit Rosenfeld and Tomer Israely and Sharon Melamed and {Abutbul Ionita}, Inbal and Dganit Danino and Dan Peer and Ofer Cohen",

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year = "2021",

month = jun,

day = "9",

doi = "10.1021/acs.nanolett.1c01284",

language = "אנגלית",

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Elia, U, Rotem, S, Bar-Haim, E, Ramishetti, S, Naidu, GS, Gur, D, Aftalion, M, Israeli, M, Bercovich-Kinori, A, Alcalay, R, Makdasi, E, Chitlaru, T, Rosenfeld, R, Israely, T, Melamed, S, Abutbul Ionita, I, Danino, D, Peer, D & Cohen, O 2021, 'Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection', Nano Letters, vol. 21, no. 11, pp. 4774-4779. https://doi.org/10.1021/acs.nanolett.1c01284

TY - JOUR

T1 - Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

AU - Elia, Uri

AU - Rotem, Shahar

AU - Bar-Haim, Erez

AU - Ramishetti, Srinivas

AU - Naidu, Gonna Somu

AU - Gur, David

AU - Aftalion, Moshe

AU - Israeli, Ma'ayan

AU - Bercovich-Kinori, Adi

AU - Alcalay, Ron

AU - Makdasi, Efi

AU - Chitlaru, Theodor

AU - Rosenfeld, Ronit

AU - Israely, Tomer

AU - Melamed, Sharon

AU - Abutbul Ionita, Inbal

AU - Danino, Dganit

AU - Peer, Dan

AU - Cohen, Ofer

PY - 2021/6/9

Y1 - 2021/6/9

N2 - The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.

AB - The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.

KW - COVID-19

KW - SARS-CoV-2

KW - ionizable lipids

KW - lipid nanoparticles

KW - mRNA vaccine

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AN - SCOPUS:85108021107

SN - 1530-6984

VL - 21

SP - 4774

EP - 4779

JO - Nano Letters

JF - Nano Letters

IS - 11

ER -

Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection

Abstract

Funding

Keywords

UN SDGs

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