Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial

• Main Authors: Sybil Tasker, Anna Wight O’Rourke, Anvar Suyundikov, Peta-Gay Jackson Booth, Stephan Bart, Vyjayanthi Krishnan, Jianfeng Zhang, Katie J. Anderson, Bertrand Georges, M. Scot Roberts
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Vaccines
• Subjects: influenza vaccine; intranasal vaccine; adenovirus vector; NasoVAX; mucosal immunity; pre-existing immunity
• Online Access: https://www.mdpi.com/2076-393X/9/3/224

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.