cyclic-guanosine-monophosphate-adenosine-monophosphate and Orthomyxoviridae-Infections

Subunit vaccines employing designer antigens such as Computationally Optimized Broadly Reactive Antigen (COBRA) hemagglutinin (HA) hold the potential to direct the immune response toward more effective and broadly-neutralizing targets on the Influenza virus. However, subunit vaccines generally require coadministration with an adjuvant to elicit a robust immune response. One such adjuvant is the stimulator of interferon genes (STING) agonist cyclic dinucleotide 3'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). We have shown that encapsulation of cGAMP in acetalated dextran (Ace-DEX) microparticles through electrospray results in significantly greater biological activity. Electrospray is a continuous manufacturing process which achieves excellent encapsulation efficiency. However, the throughput of electrospray with a single spray head is limited. Here we report the development of a multiplexed electrospray apparatus with an order of magnitude greater throughput than a single-head apparatus. Physicochemical characterization and evaluation of adjuvant activity in vitro and in vivo indicated that microparticles produced with the higher throughput process are equally suited for use as a potent vaccine adjuvant to induce a balanced immune response to COBRA HA antigens.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antibodies, Viral; Antigens; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza Vaccines; Nucleotides, Cyclic; Orthomyxoviridae Infections; Vaccines, Subunit

Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Biomimetic Materials; CD8-Positive T-Lymphocytes; Ferrets; Immunologic Memory; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Liposomes; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Nanoparticles; Nucleotides, Cyclic; Orthomyxoviridae Infections; Pulmonary Surfactants; Vaccination

Topics: Adjuvants, Immunologic; Aging; Animals; Disease Models, Animal; Drug Delivery Systems; Female; Humans; Immunosenescence; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Mice; Mice, Inbred BALB C; Nucleotides, Cyclic; Orthomyxoviridae Infections; Saponins; Transdermal Patch

Influenza vaccines for H7N9 subtype have shown low immunogenicity in human clinical trials. Using novel adjuvants might represent the optimal available option in vaccine development. In this study, we demonstrated that the using of the STING agonist cGAMP as a mucosal adjuvant is effective in enhancing humoral, cellular and mucosal immune responses of whole virus, inactivated H7N9 vaccine in mice. A single dose of immunization was able to completely protect mice against a high lethal doses of homologous virus challenge with an significant dose-sparing effect. We also found that intranasal co-administration of H7N9 vaccine with cGAMP could provide effective cross protection against H1N1, H3N2, and H9N2 influenza virus. Furthermore, cGAMP induced significantly higher nucleoprotein specific CD4

Topics: Animals; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cross Protection; Female; Immunity, Mucosal; Influenza A Virus, H7N9 Subtype; Influenza Vaccines; Interferon-gamma; Membrane Proteins; Mice; Mice, Inbred BALB C; Nucleotides, Cyclic; Orthomyxoviridae Infections; Vaccination; Vaccines, Inactivated