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

Autoři: Charles B. Stauft aff001;  Chen Yang aff001;  J. Robert Coleman aff001;  David Boltz aff002;  Chiahsuan Chin aff001;  Anna Kushnir aff001;  Steffen Mueller aff001
Působiště autorů: Codagenix, Inc., Farmingdale, New York, United States of America aff001;  Life Sciences Group, IIT Research Institute, Chicago, Illinois, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Currently, influenza vaccine manufacturers need to produce 1–5 x 107 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 1010 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 (100 or approximately 1 PFU) with CodaVax-H1N1 prevented disease after lethal challenge with wild-type H1N1. In BALB/c mice, as little as 103 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 103 PFU at preventing replication of challenge virus.

Klíčová slova:

Antibodies – Antigens – H1N1 – Influenza – Vaccination and immunization – Vaccines – Viral vaccines – Ferrets


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2019 Číslo 10
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