tetano
Editor, Senior Moderator
Vaccines (Basel)
. 2021 Nov 24;9(12):1388.
doi: 10.3390/vaccines9121388.
Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults
Joseph Eiden[SUP] 1 [/SUP], Gilad Gordon[SUP] 2 [/SUP], Carlos Fierro[SUP] 3 [/SUP], Renee Herber[SUP] 4 [/SUP], Roger Aitchison[SUP] 5 [/SUP], Robert Belshe[SUP] 6 7 [/SUP], Harry Greenberg[SUP] 8 9 [/SUP], Daniel Hoft[SUP] 6 7 [/SUP], Yasuko Hatta[SUP] 4 [/SUP], Michael J Moser[SUP] 4 [/SUP], Magdalena Tary-Lehmann[SUP] 10 [/SUP], Yoshihiro Kawaoka[SUP] 11 [/SUP], Gabriele Neumann[SUP] 11 [/SUP], Paul Radspinner[SUP] 4 [/SUP], Pamuk Bilsel[SUP] 4 [/SUP]
Affiliations
Abstract
M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (10[SUP]6[/SUP], 10[SUP]7[/SUP] or 10[SUP]8[/SUP] tissue culture infectious dose (TCID[SUB]50[/SUB])) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects.
Keywords: M2SR; clinical trial; immunity; influenza; vaccine.
. 2021 Nov 24;9(12):1388.
doi: 10.3390/vaccines9121388.
Safety and Immunogenicity of M2-Deficient, Single Replication, Live Influenza Vaccine (M2SR) in Adults
Joseph Eiden[SUP] 1 [/SUP], Gilad Gordon[SUP] 2 [/SUP], Carlos Fierro[SUP] 3 [/SUP], Renee Herber[SUP] 4 [/SUP], Roger Aitchison[SUP] 5 [/SUP], Robert Belshe[SUP] 6 7 [/SUP], Harry Greenberg[SUP] 8 9 [/SUP], Daniel Hoft[SUP] 6 7 [/SUP], Yasuko Hatta[SUP] 4 [/SUP], Michael J Moser[SUP] 4 [/SUP], Magdalena Tary-Lehmann[SUP] 10 [/SUP], Yoshihiro Kawaoka[SUP] 11 [/SUP], Gabriele Neumann[SUP] 11 [/SUP], Paul Radspinner[SUP] 4 [/SUP], Pamuk Bilsel[SUP] 4 [/SUP]
Affiliations
- PMID: 34960134
- DOI: 10.3390/vaccines9121388
Abstract
M2SR (M2-deficient single replication) is an investigational live intranasal vaccine that protects against multiple influenza A subtypes in influenza-naïve and previously infected ferrets. We conducted a phase 1, first-in-human, randomized, dose-escalation, placebo-controlled study of M2SR safety and immunogenicity. Adult subjects received a single intranasal administration with either placebo or one of three M2SR dose levels (10[SUP]6[/SUP], 10[SUP]7[/SUP] or 10[SUP]8[/SUP] tissue culture infectious dose (TCID[SUB]50[/SUB])) expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (H3N2) (24 subjects per group). Subjects were evaluated for virus replication, local and systemic reactions, adverse events (AE), and immune responses post-vaccination. Infectious virus was not detected in nasal swabs from vaccinated subjects. At least one AE (most commonly mild nasal rhinorrhea/congestion) was reported among 29%, 58%, and 83% of M2SR subjects administered a low, medium or high dose, respectively, and among 46% of placebo subjects. No subject had fever or a severe reaction to the vaccine. Influenza-specific serum and mucosal antibody responses and B- and T-cell responses were significantly more frequent among vaccinated subjects vs. placebo recipients. The M2SR vaccine was safe and well tolerated and generated dose-dependent durable serum antibody responses against diverse H3N2 influenza strains. M2SR demonstrated a multi-faceted immune response in seronegative and seropositive subjects.
Keywords: M2SR; clinical trial; immunity; influenza; vaccine.