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Chimeric Hemagglutinin-Based Influenza Virus Vaccines Induce Protective Stalk-Specific Humoral Immunity and Cellular Responses in Mice.

作者信息

Choi Angela, Bouzya Badiaa, Cortés Franco Klaus-Daniel, Stadlbauer Daniel, Rajabhathor Arvind, Rouxel Ronan N, Mainil Roland, Van der Wielen Marie, Palese Peter, García-Sastre Adolfo, Innis Bruce L, Krammer Florian, Schotsaert Michael, Mallett Corey P, Nachbagauer Raffael

机构信息

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.

GlaxoSmithKline, 1330 Rixensart, Belgium.

出版信息

Immunohorizons. 2019 Apr 1;3(4):133-148. doi: 10.4049/immunohorizons.1900022.


DOI:10.4049/immunohorizons.1900022
PMID:31032479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6485968/
Abstract

The high variation of the influenza virus hemagglutinin (HA), particularly of its immunodominant head epitopes, makes it necessary to reformulate seasonal influenza virus vaccines every year. Novel influenza virus vaccines that redirect the immune response toward conserved epitopes of the HA stalk domain should afford broad and durable protection. Sequential immunization with chimeric HAs (cHAs) that express the same conserved HA stalk and distinct exotic HA heads has been shown to elicit high levels of broadly cross-reactive Abs. In the current mouse immunization studies, we tested this strategy using inactivated split virion cHA influenza virus vaccines (IIV) without adjuvant or adjuvanted with AS01 or AS03 to measure the impact of adjuvant on the Ab response. The vaccines elicited high levels of cross-reactive Abs that showed activity in an Ab-dependent, cell-mediated cytotoxicity reporter assay and were protective in a mouse viral challenge model after serum transfer. In addition, T cell responses to adjuvanted IIV were compared with responses to a cHA-expressing live attenuated influenza virus vaccine (LAIV). A strong but transient induction of Ag-specific T cells was observed in the spleens of mice vaccinated with LAIV. Interestingly, IIV also induced T cells, which were successfully recalled upon viral challenge. Groups that received AS01-adjuvanted IIV or LAIV 4 wk before the challenge showed the lowest level of viral replication (i.e., the highest level of protection). These studies provide evidence that broadly cross-reactive Abs elicited by cHA vaccination demonstrate Fc-mediated activity. In addition, cHA vaccination induced Ag-specific cellular responses that can contribute to protection upon infection.

摘要

相似文献

[1]
Chimeric Hemagglutinin-Based Influenza Virus Vaccines Induce Protective Stalk-Specific Humoral Immunity and Cellular Responses in Mice.

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[6]
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[7]
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引用本文的文献

[1]
Long-lasting B cell convergence to distinct broadly reactive epitopes following vaccination with chimeric influenza virus hemagglutinins.

Immunity. 2025-4-8

[2]
Administration of antigenically distinct influenza viral particle combinations as an influenza vaccine strategy.

PLoS Pathog. 2025-1-22

[3]
Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

J Virol. 2024-10-22

[4]
Sequential immunization with chimeric hemagglutinin ΔNS1 attenuated influenza vaccines induces broad humoral and cellular immunity.

NPJ Vaccines. 2024-9-16

[5]
Hemagglutinin Stalk-Specific Fc-Mediated Functions Are Associated With Protection Against Influenza Illness After Seasonal Influenza Vaccination.

J Infect Dis. 2024-12-16

[6]
Flublok Quadrivalent Vaccine Adjuvanted with R-DOTAP Elicits a Robust and Multifunctional CD4 T Cell Response That Is of Greater Magnitude and Functional Diversity Than Conventional Adjuvant Systems.

Vaccines (Basel). 2024-3-7

[7]
Inactivated recombinant influenza vaccine: the promising direction for the next generation of influenza vaccine.

Expert Rev Vaccines. 2024

[8]
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[9]
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[10]
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本文引用的文献

[1]
A Live-Attenuated Prime, Inactivated Boost Vaccination Strategy with Chimeric Hemagglutinin-Based Universal Influenza Virus Vaccines Provides Protection in Ferrets: A Confirmatory Study.

Vaccines (Basel). 2018-7-25

[2]
Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention.

Expert Rev Vaccines. 2018-7-20

[3]
The influenza virus hemagglutinin head evolves faster than the stalk domain.

Sci Rep. 2018-7-11

[4]
The Influenza B Virus Hemagglutinin Head Domain Is Less Tolerant to Transposon Mutagenesis than That of the Influenza A Virus.

J Virol. 2018-7-31

[5]
Harnessing immune history to combat influenza viruses.

Curr Opin Immunol. 2018-6-8

[6]
Correlates of adjuvanticity: A review on adjuvants in licensed vaccines.

Semin Immunol. 2018-5-23

[7]
Distinct and complementary roles of CD4 T cells in protective immunity to influenza virus.

Curr Opin Immunol. 2018-4-2

[8]
A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies.

NPJ Vaccines. 2017-9-14

[9]
Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity.

NPJ Vaccines. 2017-9-8

[10]
A chimeric haemagglutinin-based influenza split virion vaccine adjuvanted with AS03 induces protective stalk-reactive antibodies in mice.

NPJ Vaccines. 2016

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