title: Rapidly produced SAM(®) vaccine against H7N9 influenza is immunogenic in mice.
abstract: The timing of vaccine availability is essential for an effective response to pandemic influenza. In 2009, vaccine became available after the disease peak, and this has motivated the development of next generation vaccine technologies for more rapid responses. The SAM(®) vaccine platform, now in pre-clinical development, is based on a synthetic, self-amplifying mRNA, delivered by a synthetic lipid nanoparticle (LNP). When used to express seasonal influenza hemagglutinin (HA), a SAM vaccine elicited potent immune responses, comparable to those elicited by a licensed influenza subunit vaccine preparation. When the sequences coding for the HA and neuraminidase (NA) genes from the H7N9 influenza outbreak in China were posted on a web-based data sharing system, the combination of rapid and accurate cell-free gene synthesis and SAM vaccine technology allowed the generation of a vaccine candidate in 8 days. Two weeks after the first immunization, mice had measurable hemagglutinin inhibition (HI) and neutralizing antibody titers against the new virus. Two weeks after the second immunization, all mice had HI titers considered protective. If the SAM vaccine platform proves safe, potent, well tolerated and effective in humans, fully synthetic vaccine technologies could provide unparalleled speed of response to stem the initial wave of influenza outbreaks, allowing first availability of a vaccine candidate days after the discovery of a new virus.
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Armin
authors.initials: A
authors.lastname: Hekele
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Archer
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Gibson
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palladino
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Brito
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Gillis R
authors.initials: GR
authors.lastname: Otten
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Brazzoli
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Scilla
authors.initials: S
authors.lastname: Buccato
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonci
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Casini
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Maione
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Qi
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Gill
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: Nicky C
authors.initials: NC
authors.lastname: Caiazza
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Urano
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: Bolyn
authors.initials: B
authors.lastname: Hubby
authors.affiliation: Chinese Center for Disease Control and Prevention , Beijing 102206, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Chinese Center for Disease Control and Prevention , Beijing 102206, China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: De Gregorio
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Mandl
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mason
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Ethan C
authors.initials: EC
authors.lastname: Settembre
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Ulmer
authors.affiliation: Synthetic Genomics, Inc., La Jolla, CA 92037, USA.
authors.forename: J
authors.initials: J
authors.lastname: Craig Venter
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dormitzer
authors.affiliation: Novartis Vaccines and Diagnostics , Siena 53100, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Novartis Vaccines and Diagnostics , Cambridge, MA 02139, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Geall
keywords: RNA vaccine; SAM vaccine; influenza; vaccine platform