tetano
Editor, Senior Moderator
Mol Ther. 2017 Apr 11. pii: S1525-0016(17)30156-9. doi: 10.1016/j.ymthe.2017.03.035. [Epub ahead of print]
[h=1]Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.[/h] Bahl K[SUP]1[/SUP], Senn JJ[SUP]2[/SUP], Yuzhakov O[SUP]1[/SUP], Bulychev A[SUP]2[/SUP], Brito LA[SUP]2[/SUP], Hassett KJ[SUP]1[/SUP], Laska ME[SUP]2[/SUP], Smith M[SUP]2[/SUP], Almarsson ?[SUP]2[/SUP], Thompson J[SUP]2[/SUP], Ribeiro AM[SUP]1[/SUP], Watson M[SUP]1[/SUP], Zaks T[SUP]2[/SUP], Ciaramella G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.
Copyright ? 2017 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] H10N8; H7N9; immunogenicity; influenza; mRNA; mRNA vaccines; pandemic; vaccines
PMID: 28457665 DOI: 10.1016/j.ymthe.2017.03.035
[h=1]Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.[/h] Bahl K[SUP]1[/SUP], Senn JJ[SUP]2[/SUP], Yuzhakov O[SUP]1[/SUP], Bulychev A[SUP]2[/SUP], Brito LA[SUP]2[/SUP], Hassett KJ[SUP]1[/SUP], Laska ME[SUP]2[/SUP], Smith M[SUP]2[/SUP], Almarsson ?[SUP]2[/SUP], Thompson J[SUP]2[/SUP], Ribeiro AM[SUP]1[/SUP], Watson M[SUP]1[/SUP], Zaks T[SUP]2[/SUP], Ciaramella G[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.
Copyright ? 2017 The Authors. Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] H10N8; H7N9; immunogenicity; influenza; mRNA; mRNA vaccines; pandemic; vaccines
PMID: 28457665 DOI: 10.1016/j.ymthe.2017.03.035