Persistent immune imprinting after XBB.1.5 COVID vaccination in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 30, 2023

Immune imprinting - also known as ‘original antigenic sin’ describes how the first exposure to a virus shapes immunological outcome of subsequent exposures antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown primarily recall cross-reactive memory B cells antibodies induced by prior mRNA with Wuhan-Hu-1 spike rather than priming naive that recognize Omicron-specific epitopes. These findings underscored strong immune resulting from repeated exposures. To understand if can be overcome, we investigated plasma antibody responses after administration updated XBB.1.5 COVID vaccine booster. Our data show booster elicits neutralizing against current variants are dominated pre-existing previously spike. results indicate persists even multiple spikes through infection, including post vaccination, which will need considered guide design future boosters.

Язык: Английский

Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine DOI Creative Commons
Kayvon Modjarrad, Ye Che, Wei Chen

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 20, 2023

ABSTRACT As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains same mRNA backbone as original modified incorporation XBB.1.5-specific sequence changes encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible predominantly open one-RBD-up state, with high affinity binding human ACE-2 receptor. When administered 4 th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose primary series naïve mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together prior experience variant-adapted preclinical clinical studies, suggest is anticipated confer protective dominant ONE-SENTENCE SUMMARY The encodes immunogen elicits more potent antibody homologous other compared thus demonstrating importance annual strain

Язык: Английский

Процитировано

14
Mapping immunodominant sites on the MERS-CoV spike glycoprotein targeted by infection-elicited antibodies in humans DOI Creative Commons
Amin Addetia, Cameron Stewart,

Albert J. Seo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 2, 2024

Abstract Middle-East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections endemic regions. Most vaccines therapeutics development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts, however, are limited by a poor understanding of antibody responses elicited infection along with their durability, fine specificity contribution distinct S antigenic sites neutralization. To address this knowledge gap, we analyzed S-directed binding neutralizing titers plasma collected from individuals infected 2017-2019 (prior COVID-19 pandemic). We observed that antibodies peak 1 6 weeks after symptom onset/hospitalization, persist for at least months, broadly neutralize camel strains. show subunit is immunodominant targeting , particularly RBD, account most activity. Antigenic site mapping revealed polyclonal frequently RBD epitopes, exposed irrespective trimer conformation, whereas 2 epitopes rare, similar SARS-CoV-2. Our data reveal unprecedented details humoral immune infection, which will guide vaccine therapeutic design.

Язык: Английский

Процитировано

5
Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine DOI Creative Commons
Kayvon Modjarrad, Ye Che, Wei Chen

и другие.

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 20, 2024

Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative original backbone, encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible, predominantly open, state, with high affinity human ACE-2 receptor. When administered as 4th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose series naive mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together real world performance suggest preclinical data predictive protective dominant

Язык: Английский

Процитировано

5
Antibody-mediated immunity to SARS-CoV-2 spike DOI
John M. Errico, Lucas J. Adams, Daved H. Fremont

и другие.

Advances in immunology, Год журнала: 2022, Номер unknown, С. 1 - 69

Опубликована: Янв. 1, 2022

Язык: Английский

Процитировано

21
Persistent immune imprinting after XBB.1.5 COVID vaccination in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 30, 2023

Immune imprinting - also known as ‘original antigenic sin’ describes how the first exposure to a virus shapes immunological outcome of subsequent exposures antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown primarily recall cross-reactive memory B cells antibodies induced by prior mRNA with Wuhan-Hu-1 spike rather than priming naive that recognize Omicron-specific epitopes. These findings underscored strong immune resulting from repeated exposures. To understand if can be overcome, we investigated plasma antibody responses after administration updated XBB.1.5 COVID vaccine booster. Our data show booster elicits neutralizing against current variants are dominated pre-existing previously spike. results indicate persists even multiple spikes through infection, including post vaccination, which will need considered guide design future boosters.

Язык: Английский

Процитировано

12