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Table 1 Selected Zika vaccines in development Mutanome draws Genentech Developer (location) Product deal In trials Immunotherapy developer BioNTech of GeneOne Life Science/Inovio GLS5700 DNA vaccine containing pre-membrane and envelope Mainz, Germany, has partnered with Roche’s (The Woodlands, Texas) protein Genentech unit to develop, manufacture and commercialize novel mRNA-based, NIAID VRC-ZKADNA085-00-VP individualized vaccines. The strategic Sanofi Purified inactivated virus vaccine collaboration combines S. – In preclinical development based Genentech’s Immunovaccine (Halifax, Nova DepoVax-Zika vaccine portfolio and research program with BioNTech’s Scotia, Canada) Adjuvant plus in liposome, suspended in oil proprietary Individualized Vaccines Against Cancer (IVAC) clinical platform that uses GeneOne Life Science GLS5700 DNA vaccine containing pre-membrane and envelope next-generation sequencing of a patient’s protein cancer to identify an array of unique GeoVax Labs (Smyrna, Georgia) GOVX-ZM01 modified vaccinia virus Ankara-virus-like particle , known as the tumor ‘mutanome’, vaccine that potentially encodes for neoantigens. These Replikins (Boston) Trivalent vaccine for Zika, dengue and Japanese encephalitis neoantigens can be exploited by making an VBI Vaccines (Cambridge, Zika eVLP bivalent vaccine with E glycoprotein and NS1 glycoprotein mRNA vaccine encoding selected neoantigens Massachusetts) for each individual tumor’s mutanome Therapeutics (Cambridge, Zika mRNA vaccine signature, triggering an immune response Massachusetts) highly specific to the tumor. The approach could result in precisely targeted cell death in a Emergent BioSolutions Zika vaccine using BARDA vaccine platform (Gaithersberg, Maryland) broad range of . “Unlike any medicine we have ever developed, virtually all cancer Ennaid Therapeutics (Alpharetta, Zika vaccine with peptide fusion inhibitors patients may potentially benefit from a custom Georgia) built ,” said James Sabry, senior Hawaii Biotech (Honolulu, Hawaii) Zika vaccine using recombinant proteins made in insect cell lines vice president and global head of Genentech partnering. “By collaborating with BioNTech Protein Sciences (Meriden, Zika vaccine based on recombinant variants of E protein on this cutting edge approach, we hope to truly Connecticut) advance cancer treatments by using a common VLP Therapeutics (Gaithersberg, Zika vaccine using i-alpha VLP technology molecular backbone—mRNA—that is uniquely Maryland) tailored to an individual patient.” Genentech Valneva (Lyon, France) VLA1601 inactivated Zika vaccine agreed to pay BioNTech $310 million in upfront and near-term milestone payments, and the Vaxart (S. San Francisco, ) Non-replicating adenovirus type-5-vector-based Zika vaccine two companies will share all development Atheric Pharmaceutical (Troy, Repurposed marketed drugs costs and any potential profits, with BioNTech Virginia) retaining the right to co-promote certain Bharat Biotech (Genome Valley, ZikaVAC inactivated virus products that arise from the agreement in Hyderabad, India) ZikaVAC recombinant vaccine using viral surface the US, Germany and several other markets. BARDA, The Biomedical Advanced Research and Development Authority; eVLP, enveloped virus like particle. Source: The deal with Genentech follows previously BioMedTracker, clinicaltrials.gov, company websites announced collaborations with Bayer for new mRNA vaccines and therapeutics for animal Tang at Florida State University in Tallahassee, antiviral activity. The team are “going deep and health applications, and Sanofi for cancer who had a small NIH-funded program on going broad,” says Tang, gearing up to conduct immunotherapies. dengue. In January, when his group was pre- preclinical studies with the repurposed drug paring to make a large batch of dengue virus, Niclocide (niclosamide), approved by the US he switched gears immediately to Zika. Between Food and Drug Administration for treating then and now, his group, in collaboration with worm infections in humans and livestock, after neuroscientists Hongjun Song and Guo-Li they found it inhibited Zika replication in their Ming at Johns Hopkins University in Baltimore, screen. The researchers have also developed a © 2016 America, Inc., part of Springer Nature. All rights reserved. All rights part Nature. of Springer Inc., America, Nature © 2016 and Wei Zheng, at NIH’s National Center for specific assay for Zika replication, which they Advancing Translational Sciences (NCATS), have used for rescreening the compound library “The disappearance of a few published a series of papers relating to the (unpublished data). Tang has pieced together species, while a pity, does not bring

virus’s effects on neuronal cells (neural progeni- internal funding from his university with some a whole ecosystem crashing down.” Evolutionary biologist Olivia Judson refers tor cells, astrocytes and brain organoids devel- external grants to support this work and, in to attempts by the biotech company oped from induced pluripotent stem cells) (Cell August, a pharma holding company based in Oxitec to eliminate Zika-transmitting 165, 1238–1254, 2016). The team also identified West Des Moines, Iowa, Spotlight Innovations, mosquitoes through engineering a fatal small molecules that inhibit Zika virus repli- stepped in with several years of funding. The genetic trait into male Aedes aegypti. cation from an NCATS repurposing library of agreement gives the company the right to (BloombergBusinessWeek, 6 October 2016) 6,000 compounds (Nat. Med. 22, 1101–1107, license any intellectual property that comes “I don’t know what the precedent is for 2016). Their hits fall into two categories, inhibi- from the sponsorship. submitting three negative studies [to the tors of Zika infection in human central nervous Similarly, Barouch’s team began work in early FDA].” Phyllis Ferrell, vice president of Lilly’s Alzheimer’s division, speculates on 2016 following reports about the epidemic in system cells and inhibitors of Zika-induced cas- the chances of approval for its Alzheimer’s pase activity, which causes neuronal cell death. Brazil and the World Health Organization’s disease treatment, monoclonal anti-amyloid Tang and collaborators are moving forward, declaring a global health emergency. With the antibody (solanezumab), that has so far testing compounds that either protect neu- help of three Brazilian post-docs working in his failed in clinical trials. (STAT News, rons from Zika-virus-induced caspase or have laboratory and their contacts, they were able to 13 October 2016)

NATURE VOLUME 34 NUMBER 11 NOVEMBER 2016 1085