4.5 Article

Novel TLR4 adjuvant elicits protection against homologous and heterologous Influenza A infection

期刊

VACCINE
卷 39, 期 36, 页码 5205-5213

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2021.06.085

关键词

Vaccine; Influenza; Adjuvant; TLR4 agonist; Cross-protection

资金

  1. U.S. Army's Long Term Health and Education Training Program
  2. BARDA [ASPR-20-01495]
  3. NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) [HHSN272201400008C]
  4. Collaborative Influenza Vaccine Innovation Centers (CIVIC) [75N93019C00051]
  5. [T32 AI095190]

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The study shows that TLR4 immunostimulatory molecules BECC438 and BECC470 are superior IAV vaccine adjuvants, allowing for antigen sparing, eliciting a more balanced immune response, and providing protection against heterologous IAV strains.
Influenza A virus (IAV) is a leading cause of respiratory disease worldwide often resulting in hospitaliza-tion or death. In this study, TLR4 immunostimulatory molecules, Bacterial Enzymatic Combinatorial Chemistry (BECC) 438 and BECC470 were found to be superior IAV vaccine adjuvants when compared to the classic adjuvant alhydrogel (alum) and Phosphorylated Hexa-Acyl Disaccharide (PHAD), a synthetic TLR4 agonist. BECC molecules allow for antigen sparing of a recombinant HA (rHA) protein, elicit a more balanced IgG1/IgG2a response, and were protective in a prime only dosing schedule. Importantly, BECC molecules afford protection from a heterologous IAV strain demonstrating that a cross-protective influ-enza vaccine is possible when the antigen is effectively adjuvanted. (c) 2021 Elsevier Ltd. All rights reserved.

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