Annual influenza vaccination greatly reduces morbidity and mortality, but effectiveness remains sub-optimal. Weaknesses of current vaccines include low effectiveness against mismatched strains, lack of mucosal and other effective tissue-resident immune responses, weak cellular immune responses, and insufficiently durable immune responses. The safety and immunogenicity of NasoVAX, a monovalent intranasal influenza vaccine based on a replication-deficient adenovirus type 5 platform, were evaluated in a placebo-controlled single ascending-dose study. Sixty healthy adults (18–49 years) received a single intranasal dose of 1×109 viral particles (vp), 1 × 1010 vp, or 1 × 1011 vp of NasoVAX or placebo. NasoVAX was well-tolerated and elicited robust influenza-specific systemic and mucosal immune responses. The highest NasoVAX dose and the approved Fluzone® influenza vaccine elicited comparable hemagglutination inhibition (HAI) geometric mean titers (152.8 vs. 293.4) and microneutralization (MN) geometric mean titers (142.5 vs. 162.8), with NasoVAX HAI titers maintained more than 1-year on average following a single dose. Hemagglutinin-specific T cells responses were also documented in peripheral mononuclear cell (PBMC) preparations. Consistent with the intranasal route of administration, NasoVAX elicited antigen-specific mucosal IgA responses in the nasopharyngeal cavity with an increase of approximately 2-fold over baseline GMT at the mid- and high-doses. In summary, NasoVAX appeared safe and elicited a broad immune response, including humoral, cellular, and mucosal immunity, with no impact of baseline anti-adenovirus antibody at the most immunogenic dose.
BackgroundNasoVAX is a replication-deficient adenovirus-based vaccine designed to express influenza hemagglutinin in nasal epithelial cells when given as a nasal spray. In preclinical studies, NasoVAX was associated with divergent strain protection. Prior preclinical and clinical studies with the vector demonstrated lack of impact from baseline adenovirus immunity.MethodsSixty healthy adults were randomized to an A/California 2009-based monovalent NasoVAX formulation at doses of 109, 1010, or 1011 viral particles or saline placebo, all given as a 0.25 mL nasal spray in each nostril. Subjects were followed for safety, including solicited local and systemic side effects. Immune measures included hemagglutination inhibition (HAI) and neutralizing antibody (MN) at days 1, 15, 29, 90, and 180, and γ-interferon ELISpot at day 1 and 8. A parallel cohort of 20 similar subjects were dosed with Fluzone® injectable influenza vaccine containing an A/California 2009 component and had assessments at the same timepoints. The laboratory was blind to treatment assignment for these comparator samples.ResultsNasoVAX was well tolerated with no serious adverse events and no fever. Solicited symptoms such as nasal congestion, sore throat, and headache did not increase with dose and were not statistically different than placebo. Available immune response data are shown below.GroupNasoVAX (109 vp)NasoVAX (1010 vp)NasoVAX (1011 vp)Fluzone®PlaceboSeroprotection Rate at Day 29 (≥1:40 HAI)80%100%100%95%53%(95% CIs)(51.9%, 95.7%)(78.2%, 100.0%)(78.2%, 100.0%)(75.1%, 99.9%)(26.6%, 78.7%)MN Responder Rate at Day 29 (2-fold rise)40%47%73%70%0%(95% CIs)(16.3%, 67.7%)(21.3%, 73.4%)(44.9%, 92.2%)(45.7%, 88.1%)(0.0%, 21.8%)Median ELISpot Day 8 SFC/106 PBMC58.012.0307.555.50.0(95% CIs)(5.31, 110.69)(0.0, 60.36)(2.15, 612.78)(4.12, 106.87)(0.0, 38.49)ConclusionNasoVAX intranasal influenza vaccine was well tolerated and elicited comparable antibody responses and nearly 6-fold higher cellular immune responses than a licensed injectable vaccine.Disclosures S. Tasker, Altimmune, Inc: Employee and Shareholder, Salary. V. Krishnan, Altimmune, Inc.: Employee and Shareholder, Salary. S. Bart, Altimmune, Inc.: Research Contractor, fee for research services. A. Suyundikov, Altimmune, Inc.: Employee, Salary. P. G. Booth, Altimmune, Inc.: Research Contractor, fee for research services. A. Wight O’Rourke, Altimmune, Inc.: Employee and Shareholder, Salary. J. Zhang, Altimmune, Inc.: Employee and Shareholder, Salary. B. Georges, Altimmune, Inc.: Employee and Shareholder, Salary. S. Roberts, Altimmune, Inc.: Employee and Shareholder, Salary.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.