Impact of Imprinted Immunity Induced by mRNA Vaccination in an Experimental Animal Model

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of “imprinted immunity” suggests that individuals vaccinat...

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Published inThe Journal of infectious diseases Vol. 228; no. 8; pp. 1060 - 1065
Main Authors Fujita, Shigeru, Uriu, Keiya, Pan, Lin, Nao, Naganori, Tabata, Koshiro, Kishimoto, Mai, Itakura, Yukari, Sawa, Hirofumi, Kida, Izumi, Tamura, Tomokazu, Fukuhara, Takasuke, Ito, Jumpei, Matsuno, Keita, Sato, Kei
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 18.10.2023
Subjects
Animal models
Antiviral drugs
Brief Report
Coronaviruses
Humoral immunity
Immunity
mRNA
Nanoparticles
Severe acute respiratory syndrome coronavirus 2
Vaccines
SARS-CoV-2
omicron
imprinted immunity
mRNA vaccine
Omicron
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Summary:Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of “imprinted immunity” suggests that individuals vaccinated with ancestral virus-based vaccines may not develop effective immunity against newly emerging Omicron subvariants, such as BQ.1.1 and XBB.1. In this study, we investigated this possibility using hamsters. Although natural infection induced effective antiviral immunity, breakthrough infections in hamsters with BQ.1.1 and XBB.1 Omicron subvariants after receiving the 3-dose mRNA-lipid nanoparticle vaccine resulted in only faintly induced humoral immunity, supporting the possibility of imprinted immunity. The emergence of SARS-CoV-2 Omicron XBB subvariants raises vaccine effectiveness concerns. Our hamster model demonstrated that ancestral virus-based vaccines failed to produce effective neutralizing antibodies against Omicron subvariants (eg, BQ.1.1, XBB.1) during breakthrough infections, supporting the concept of imprinted immunity.
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Potential conflicts of interest. SF has an honorarium for a lecture from ROYAL CANIN JAPON, Inc. NN has consulting fees from Fasmac Co., Ltd. HS has royalties from Shionogi & Co., Ltd., honoraria for lectures from Tenshi College, and is a coinventor of a patent (JP 7236065 B1, “Pharmaceutical composition containing triazine derivative”). JI has consulting fees and honoraria for lectures from Takeda Pharmaceutical Co. Ltd. KS has consulting fees from Moderna Japan Co., Ltd. and Takeda Pharmaceutical Co. Ltd. and honoraria for lectures from Gilead Sciences, Inc., Moderna Japan Co., Ltd., and Shionogi & Co., Ltd. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
K. M. and K. S. contributed equally to this study.
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiad230