High- and low-molecular-weight chitosan act as adjuvants during single-dose influenza A virus protein vaccination through distinct mechanisms

Anna T. Lampe, Eric J. Farris, Deborah M. Brown, Angela K. Pannier

Research output: Contribution to journalArticlepeer-review

Abstract

The investigation of new adjuvants is essential for the development of efficacious vaccines. Chitosan (CS), a derivative of chitin, has been shown to act as an adjuvant, improving vaccine-induced immune responses. However, the effect of CS molecular weight (MW) on this adjuvanticity has not been investigated, despite MW having been shown to impact CS biological properties. Here, two MW variants of CS were investigated for their ability to enhance vaccine-elicited immune responses in vitro and in vivo, using a single-dose influenza A virus (IAV) protein vaccine model. Both low-molecular-weight (LMW) and high-molecular-weight (HMW) CS-induced interferon regulatory factor pathway signaling, antigen-presenting cell activation, and cytokine messenger RNA (mRNA) production, with LMW inducing higher mRNA levels at 24 h and HMW elevating mRNA responses at 48 h. LMW and HMW CS also induced adaptive immune responses after vaccination, indicated by enhanced immunoglobulin G production in mice receiving LMW CS and increased CD4 interleukin 4 (IL-4) and IL-2 production in mice receiving HMW CS. Importantly, both LMW and HMW CS adjuvantation reduced morbidity following homologous IAV challenge. Taken together, these results support that LMW and HMW CS can act as adjuvants, although this protection may be mediated through distinct mechanisms based on CS MW.

Original languageEnglish (US)
Pages (from-to)1224-1243
Number of pages20
JournalBiotechnology and Bioengineering
Volume118
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • IRF signaling
  • adaptive immunity
  • adjuvants
  • chitosan
  • innate immunity

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Fingerprint

Dive into the research topics of 'High- and low-molecular-weight chitosan act as adjuvants during single-dose influenza A virus protein vaccination through distinct mechanisms'. Together they form a unique fingerprint.

Cite this