tetano
Editor, Senior Moderator
Vaccines (Basel)
. 2021 Mar 5;9(3):224.
doi: 10.3390/vaccines9030224.
Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial
Sybil Tasker[SUP] 1 2 [/SUP], Anna Wight O'Rourke[SUP] 1 3 [/SUP], Anvar Suyundikov[SUP] 1 [/SUP], Peta-Gay Jackson Booth[SUP] 4 [/SUP], Stephan Bart[SUP] 4 [/SUP], Vyjayanthi Krishnan[SUP] 1 [/SUP], Jianfeng Zhang[SUP] 1 [/SUP], Katie J Anderson[SUP] 1 5 [/SUP], Bertrand Georges[SUP] 1 [/SUP], M Scot Roberts[SUP] 1 [/SUP]
Affiliations
Abstract
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?10[SUP]9[/SUP] viral particles (vp), 1 ? 10[SUP]10[/SUP] vp, or 1 ? 10[SUP]11[/SUP] 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[SUP]?[/SUP] 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.
Keywords: NasoVAX; adenovirus vector; influenza vaccine; intranasal vaccine; mucosal immunity; pre-existing immunity.
. 2021 Mar 5;9(3):224.
doi: 10.3390/vaccines9030224.
Safety and Immunogenicity of a Novel Intranasal Influenza Vaccine (NasoVAX): A Phase 2 Randomized, Controlled Trial
Sybil Tasker[SUP] 1 2 [/SUP], Anna Wight O'Rourke[SUP] 1 3 [/SUP], Anvar Suyundikov[SUP] 1 [/SUP], Peta-Gay Jackson Booth[SUP] 4 [/SUP], Stephan Bart[SUP] 4 [/SUP], Vyjayanthi Krishnan[SUP] 1 [/SUP], Jianfeng Zhang[SUP] 1 [/SUP], Katie J Anderson[SUP] 1 5 [/SUP], Bertrand Georges[SUP] 1 [/SUP], M Scot Roberts[SUP] 1 [/SUP]
Affiliations
- PMID: 33807649
- DOI: 10.3390/vaccines9030224
Abstract
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?10[SUP]9[/SUP] viral particles (vp), 1 ? 10[SUP]10[/SUP] vp, or 1 ? 10[SUP]11[/SUP] 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[SUP]?[/SUP] 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.
Keywords: NasoVAX; adenovirus vector; influenza vaccine; intranasal vaccine; mucosal immunity; pre-existing immunity.