tetano
Editor, Senior Moderator
J Infect Dis
. 2021 Jul 29;jiab374.
doi: 10.1093/infdis/jiab374. Online ahead of print.
Single Replication M2SR Influenza Vaccine Induced Immune Responses Associated with Protection Against Human Challenge with Highly Drifted H3N2 Influenza Strain
Joseph Eiden[SUP] 1 [/SUP], Bram Volckaert[SUP] 2 [/SUP], Oleg Rudenko[SUP] 2 [/SUP], Roger Aitchison[SUP] 3 [/SUP], Renee Herber[SUP] 4 [/SUP], Robert Belshe[SUP] 5 [/SUP], Harry Greenberg[SUP] 6 [/SUP], Kathleen Coelingh[SUP] 7 [/SUP], David Marshall[SUP] 4 [/SUP], Yoshihiro Kawaoka[SUP] 8 [/SUP], Gabriele Neumann[SUP] 8 [/SUP], Pamuk Bilsel[SUP] 4 [/SUP]
Affiliations
Abstract
Background: Current influenza vaccines are strain-specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mis-matched to circulating virus. The novel influenza vaccine candidate, M2SR (M2-deficient Single Replication), induces a broad, multi-effector immune response.
Methods: A phase 2 challenge study was conducted to assess efficacy of M2SR vaccine expressing HA and NA from A/Brisbane/10/2007 (H3N2, clade 1). Four weeks after vaccination subjects were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b), and assessed for infection and clinical symptoms.
Results: Adverse events following vaccination were mild and similar in frequency between placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.
Conclusions: Subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus.
Keywords: H3N2; challenge; drift; influenza; vaccine.
. 2021 Jul 29;jiab374.
doi: 10.1093/infdis/jiab374. Online ahead of print.
Single Replication M2SR Influenza Vaccine Induced Immune Responses Associated with Protection Against Human Challenge with Highly Drifted H3N2 Influenza Strain
Joseph Eiden[SUP] 1 [/SUP], Bram Volckaert[SUP] 2 [/SUP], Oleg Rudenko[SUP] 2 [/SUP], Roger Aitchison[SUP] 3 [/SUP], Renee Herber[SUP] 4 [/SUP], Robert Belshe[SUP] 5 [/SUP], Harry Greenberg[SUP] 6 [/SUP], Kathleen Coelingh[SUP] 7 [/SUP], David Marshall[SUP] 4 [/SUP], Yoshihiro Kawaoka[SUP] 8 [/SUP], Gabriele Neumann[SUP] 8 [/SUP], Pamuk Bilsel[SUP] 4 [/SUP]
Affiliations
- PMID: 34323977
- DOI: 10.1093/infdis/jiab374
Abstract
Background: Current influenza vaccines are strain-specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mis-matched to circulating virus. The novel influenza vaccine candidate, M2SR (M2-deficient Single Replication), induces a broad, multi-effector immune response.
Methods: A phase 2 challenge study was conducted to assess efficacy of M2SR vaccine expressing HA and NA from A/Brisbane/10/2007 (H3N2, clade 1). Four weeks after vaccination subjects were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b), and assessed for infection and clinical symptoms.
Results: Adverse events following vaccination were mild and similar in frequency between placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.
Conclusions: Subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus.
Keywords: H3N2; challenge; drift; influenza; vaccine.