Preliminary evaluation of adjuvant effects of cyclic dinucleotides (CDN) on immune responses to nasal spray influenza vaccine

Abstract

Objective To analyze the immunostimulatory effects of cyclic dinucleotides (CDN) on immune responses to a nasal spray influenza split virus vaccine and to evaluate its potential as a mucosal adjuvant. Methods A H1N1 influenza split virus vaccine combined with different CDN was used for mouse immunization. Each mouse was intranasally immunized twice with 4.5 μg of hemagglutinin (HA) and 10 μg of CDN with an interval of 21 d. Titers of hemagglutination inhibition (HI) antibodies in serum, secretory IgA (sIgA) in bronchoalveolar lavage fluid and IgG in serum were detected 21 d after the last immunization. Immunostimulatory activities of different CDN were compared. Effects of cyclic di-GMP (c-di-GMP) and chitosan (CSN) on the immunogenicity of H1N1 and H7N9 influenza split vaccines were analyzed and compared. H1N1 influenza split vaccine combined with c-di-GMP or CSN was used to immunize mice. Three weeks after the last immunization, these mice were challenged with 10 times the median lethal dose (LD50) of A/Puerto Rico/8/34 (H1N1) influenza virus. Survival rates of the mice were observed for 14 d. Results All three CDN induced high levels of HI antibodies and IgG in serum and sIgA in BALF. HI antibody seroconversion rates were also higher than those of the control groups. c-di-GMP was superior to CSN in enhancing the immunogenicity of H1N1 and H7N9 antigens as higher titers of HI antibodies in serum and sIgA in BALF were induced. Conclusions CDN could enhance the immunogenicity of influenza antigens with better efficacy than CSN adjuvant. Key words: Cyclic dinucleotide; Adjuvant; Chitosan; Immunogenicity