Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59

Abstract

Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA) has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV) via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI) methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs) for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice

“…), and an influenza vaccine containing Escherichia coli heat-labile enterotoxin (LT) was linked to Bell’s palsy ( 9 ). Nevertheless, new promising candidates, such as members of the cyclic-di-nucleotide family among others, are under development ( 10 , 11 ). The cyclic-di-nucleotides are second-messenger molecules in bacteria and archea ( 12 , 13 ) and the innate immune system senses them via STING (stimulator of interferon genes) and DDX41 [DEAD (aspartate-glutamate-alanine-aspartate)-box helicase 41] ( 14 , 15 ).…”

CD8 + T‐cell percentage increases in diffuse large B‐cell lymphoma patients receiving mannatide combined with standard regimens

“…In the study of Wang W et al, 13 MT in combination with E75 peptide significantly induced splenocytes to produce IFN‐γ in mice. In the study of Ren ST, 14 MT significantly boosted IFN‐γ production by splenic lymphocytes after vaccine antigen stimulation, indicating that MT could promote the cell‐mediated immune response after intranasal vaccination.…”

Current and Next Generation Vaccines Against Influenza

“…Intranasal vaccination is an attractive route as a needle-free vaccine delivery method. When inactivated influenza vaccines were administered intranasally with an appropriate adjuvant, IgA was induced in the respiratory tract [23]. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines showed protection against infection of influenza virus [24].…”