PlOS ONE: Live-attenuated H1N1 influenza vaccine candidate displays potent efficacy in mice and ferrets

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[h=1]Live-attenuated H1N1 influenza vaccine candidate displays potent efficacy in mice and ferrets[/h]

• Charles B. Stauft,
• Chen Yang,
• J. Robert Coleman,
• David Boltz,
• Chiahsuan Chin,
• Anna Kushnir,
• Steffen Mueller

• Published: October 14, 2019
• https://doi.org/10.1371/journal.pone.0223784

Currently, influenza vaccine manufacturers need to produce 1–5 x 10[SUP]7[/SUP] PFU of each vaccine strain to fill one dose of the current live-attenuated-influenza-vaccine (LAIV). To make a single dose of inactivated vaccine (15 ug of each hemagglutinin), the equivalent of 10[SUP]10[/SUP] PFU of each vaccine strains need to be grown. This high dose requirement is a major drawback for manufacturing as well as rapidly sourcing sufficient doses during a pandemic. Using our computer-aided vaccine platform Synthetic Attenuated Virus Engineering (SAVE), we created a vaccine candidate against pandemic H1N1 A/CA/07/2009 (CodaVax-H1N1) with robust efficacy in mice and ferrets, and is protective at a much lower dose than the current LAIV. CodaVax-H1N1 is currently in Phase I/II clinical trials. The hemagglutinin (HA) and neuraminidase (NA) gene segments of A/California/07/2009 (H1N1) (CA07) were “de-optimized” and a LAIV was generated ex silico using DNA synthesis. In DBA/2 mice, vaccination at a very low dose (10[SUP]0[/SUP] or approximately 1 PFU) with CodaVax-H1N1 prevented disease after lethal challenge with wild-type H1N1. In BALB/c mice, as little as 10[SUP]3[/SUP] PFU was protective against lethal challenge with mouse-adapted H1N1. In ferrets, CodaVax-H1N1 was more potent compared to currently licensed LAIV and still effective at a low dose of 10[SUP]3[/SUP] PFU at preventing replication of challenge virus.

full article

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223784