Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

Baoling Ying; Suzanne M. Scheaffer; Bradley Whitener; Chieh Yu Liang; Oleksandr Dmytrenko; Samantha Mackin; Kai Wu; Diana Lee; Laura E. Avena; Zhenlu Chong; James Brett Case; Ling Zhi Ma; Thu T.M. Kim; Caralyn E. Sein; Angela Woods; Daniela Montes Berrueta; Gwo Yu Chang; Guillaume Stewart-Jones; Isabella Renzi; Yen Ting Lai; Agata Malinowski; Andrea Carfi; Sayda M. Elbashir; Darin K. Edwards; Larissa B. Thackray; Michael S. Diamond

doi:10.1016/j.cell.2022.03.037

Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

Baoling Ying, Suzanne M. Scheaffer, Bradley Whitener, Chieh Yu Liang, Oleksandr Dmytrenko, Samantha Mackin, Kai Wu, Diana Lee, Laura E. Avena, Zhenlu Chong, James Brett Case, Ling Zhi Ma, Thu T.M. Kim, Caralyn E. Sein, Angela Woods, Daniela Montes Berrueta, Gwo Yu Chang, Guillaume Stewart-Jones, Isabella Renzi, Yen Ting LaiAgata Malinowski, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael S. Diamond

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

57 Scopus citations

Abstract

The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.

Original language	English
Pages (from-to)	1572-1587.e11
Journal	Cell
Volume	185
Issue number	9
DOIs	https://doi.org/10.1016/j.cell.2022.03.037
State	Published - Apr 28 2022

Keywords

Omicron
SARS-CoV-2
antibody
booster
immunity
mRNA vaccine
mice
neutralization
pathogenesis

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10.1016/j.cell.2022.03.037

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Ying, B., Scheaffer, S. M., Whitener, B., Liang, C. Y., Dmytrenko, O., Mackin, S., Wu, K., Lee, D., Avena, L. E., Chong, Z., Case, J. B., Ma, L. Z., Kim, T. T. M., Sein, C. E., Woods, A., Berrueta, D. M., Chang, G. Y., Stewart-Jones, G., Renzi, I., ... Diamond, M. S. (2022). Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice. Cell, 185(9), 1572-1587.e11. https://doi.org/10.1016/j.cell.2022.03.037

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title = "Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice",

abstract = "The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.",

keywords = "Omicron, SARS-CoV-2, antibody, booster, immunity, mRNA vaccine, mice, neutralization, pathogenesis",

author = "Baoling Ying and Scheaffer, {Suzanne M.} and Bradley Whitener and Liang, {Chieh Yu} and Oleksandr Dmytrenko and Samantha Mackin and Kai Wu and Diana Lee and Avena, {Laura E.} and Zhenlu Chong and Case, {James Brett} and Ma, {Ling Zhi} and Kim, {Thu T.M.} and Sein, {Caralyn E.} and Angela Woods and Berrueta, {Daniela Montes} and Chang, {Gwo Yu} and Guillaume Stewart-Jones and Isabella Renzi and Lai, {Yen Ting} and Agata Malinowski and Andrea Carfi and Elbashir, {Sayda M.} and Edwards, {Darin K.} and Thackray, {Larissa B.} and Diamond, {Michael S.}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

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day = "28",

doi = "10.1016/j.cell.2022.03.037",

language = "English",

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Ying, B, Scheaffer, SM, Whitener, B, Liang, CY, Dmytrenko, O, Mackin, S, Wu, K, Lee, D, Avena, LE, Chong, Z , Case, JB, Ma, LZ, Kim, TTM, Sein, CE, Woods, A, Berrueta, DM, Chang, GY, Stewart-Jones, G, Renzi, I, Lai, YT, Malinowski, A, Carfi, A, Elbashir, SM, Edwards, DK, Thackray, LB & Diamond, MS 2022, 'Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice', Cell, vol. 185, no. 9, pp. 1572-1587.e11. https://doi.org/10.1016/j.cell.2022.03.037

TY - JOUR

T1 - Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

AU - Ying, Baoling

AU - Scheaffer, Suzanne M.

AU - Whitener, Bradley

AU - Liang, Chieh Yu

AU - Dmytrenko, Oleksandr

AU - Mackin, Samantha

AU - Wu, Kai

AU - Lee, Diana

AU - Avena, Laura E.

AU - Chong, Zhenlu

AU - Case, James Brett

AU - Ma, Ling Zhi

AU - Kim, Thu T.M.

AU - Sein, Caralyn E.

AU - Woods, Angela

AU - Berrueta, Daniela Montes

AU - Chang, Gwo Yu

AU - Stewart-Jones, Guillaume

AU - Renzi, Isabella

AU - Lai, Yen Ting

AU - Malinowski, Agata

AU - Carfi, Andrea

AU - Elbashir, Sayda M.

AU - Edwards, Darin K.

AU - Thackray, Larissa B.

AU - Diamond, Michael S.

PY - 2022/4/28

Y1 - 2022/4/28

N2 - The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.

AB - The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.

KW - Omicron

KW - SARS-CoV-2

KW - antibody

KW - booster

KW - immunity

KW - mRNA vaccine

KW - mice

KW - neutralization

KW - pathogenesis

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AN - SCOPUS:85127635381

SN - 0092-8674

VL - 185

SP - 1572-1587.e11

JO - Cell

JF - Cell

IS - 9

ER -

Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice

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Keywords

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