Simultaneous formulation of influenza vaccine and chitosan nanoparticles within CpG oligodesoxi nucleotides leads to dose-sparing and protects against lethal challenge in the mouse model

Abstract

Lack of efficient delivery systems for transporting antigenic molecules to the cytosol of antigen-presenting cells presents a major obstacle for antigen uptake by immune cells. To this end, influenza whole inactivated virus vaccines were formulated with chitosan nanoparticles and CpG oligonucleotide as a biodegradable delivery system and a Th1-specific adjuvant, respectively. Intradermal injections of a single high dose and low dose of formulated candidate vaccines were carried out. Thirty days after injection, cell proliferation assay (MTT), IFN-gamma and IL-4 ELISpot assays were conducted. Sera samples were collected 21 days after immunization to measure IgG1 and IgG2a levels. In addition, the mice challenged with mouse-adopted virus were monitored for weight loss. The results show a significant stimulation of both humoral and cellular immunities; also, weight gain and a decrease in mortality in the mice receiving both dosages of inactivated influenza virus vaccines with CpG and Chitosan coating were observed. Based on the results, it can be concluded that formulation of inactivated influenza virus with CpG and its delivery by chitosan as low-dose can return the same results as with high-dose balanced between cellular and humeral immune responses. This formulation could potentially lead to a significant saving in vaccine production.