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

[tetano]

Biotechnol Bioeng


. 2020 Dec 7.
doi: 10.1002/bit.27647. Online ahead of print.
High and low molecular weight chitosan act as adjuvants during single dose influenza A virus protein vaccination through distinct mechanisms


Anna T Lampe ^{1 2} , Eric J Farris ³ , Deborah M Brown ^{1 2} , Angela K Pannier ^{2 3}



Affiliations

• PMID: 33289090
• DOI: 10.1002/bit.27647

Abstract

The investigation of new adjuvants is essential for 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 MW (LMW) and high MW (HMW) CS induced IRF pathway signaling, antigen presenting cell (APC) activation, and cytokine 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 IgG production in mice receiving LMW CS and increased CD4 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. This article is protected by copyright. All rights reserved.

Keywords: Adaptive immunity; Adjuvants; Chitosan; IRF signaling; Innate immunity.