Cited by 134Influenza Virus Research StudiesImmunotherapy and Immune ResponsesImmune responses and vaccinations

Induction of robust B cell responses after influenza mRNA vaccination Is accompanied by circulating hemagglutinin-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells

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Lindgren, Gustaf, Ols, Sebastian, Liang, Frank, Thompson, Elizabeth A., Lin, Ang, Hellgren, Fredrika, Bahl, Kapil, John, Shinu +6 more·2017·Frontiers in Immunology

Abstract

Modified mRNA vaccines have developed into an effective and well-tolerated vaccine platform that offers scalable and precise antigen production. Nevertheless, the immunological events leading to strong antibody responses elicited by mRNA vaccines are largely unknown. In this study, we demonstrate that protective levels of antibodies to hemagglutinin were induced after two immunizations of modified non-replicating mRNA encoding influenza H10 encapsulated in lipid nanoparticles (LNP) in non-human primates. While both intradermal (ID) and intramuscular (IM) administration induced protective titers, ID delivery generated this response more rapidly. Circulating H10-specific memory B cells expanded after each immunization, along with a transient appearance of plasmablasts. The memory B cell pool waned over time but remained detectable throughout the 25-week study. Following prime immunization, H10-specific plasma cells were found in the bone marrow and persisted over time. Germinal centers were formed in vaccine-draining lymph nodes along with an increase in circulating H10-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells, a population shown to correlate with high avidity antibody responses after seasonal influenza vaccination in humans. Collectively, this study demonstrates that mRNA/LNP vaccines potently induce an immunological repertoire associated with the generation of high magnitude and quality antibodies.

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  • Intramuscular delivery of 1mΨ-modified mRNA vaccines results in rapid and potent induction of follicular T helper cells (Tfh).

    “several studies have shown that i.m. delivery of 1mΨ-modified mRNA vaccines results in the rapid and potent induction of follicular T helper cells (Tfh) [71,72].”

    From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [71]

  • Robust and sustained antigen expression of nucleoside-modified mRNA is associated with more optimal antibody responses compared to unmodified mRNA.

    “Additionally, the robust and sustained antigen expression of nucleoside-modified mRNA was associated with more optimal antibody responses compared to unmodified mRNA [12,13].”

    From Three decades of messenger RNA vaccine development (2019) · cites this paper as [13]

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Authors
Lindgren, G., Ols, S., Liang, F., Thompson, E. A., Lin, A., Hellgren, F., Bahl, K., John, S., Yuzhakov, O., Hassett, K. J., Brito, L. A., Salter, H., Ciaramella, G., & Loré, K.
Affiliations
  • Karolinska Institutet (SE)
  • Moderna Therapeutics (United States) (US)
Corresponding author
Loré, Karin
Venue
Frontiers in Immunology
Published
2017-11-13
Volume
8
Pages
1539-1539
ISSN
1664-3224 (ISSN-L)
OpenAlex
W2767992446
Cited by
132
References
44
Citations by year
2026: 3 · 2025: 13 · 2024: 9 · 2023: 16 · 2022: 25 · 2021: 37 · 2020: 15 · 2019: 10 · 2018: 4
FWCI
6.21
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Karolinska Institutet
  • Vetenskapsrådet
  • China Scholarship Council
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
T follicular helper cells, ICOS, PD-1, CXCR3, memory B cells, plasma cells, germinal center, intradermal vaccination, intramuscular vaccination, non-human primates, vaccine immunogenicity

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