Inovio Pharmaceuticals has announced that its DNA-based Zika virus vaccine GLS-5700 generated robust antigen-specific antibody responses in a first-in-man phase 1 trial. In initial testing, Zika-naïve subjects in both low-dose and high-dose vaccine groups demonstrated Zika antigen-specific antibody responses after one or two vaccinations. In addition, the vaccine was well tolerated, and no significant safety concerns were noted in any of the 40 subjects for up to 14 weeks after the initiation of dosing––the latest available data from the study.
The vaccine is injected along with a brief low-voltage electronic pulse that induces cell membranes to open, making them more receptive—theoretically––to accepting the vaccine’s genetic material.
The ongoing, open-label, dose-ranging study of GLS-5700 in healthy adult volunteers is evaluating the safety, tolerability, and induction and persistence of Zika-specific antibody and T-cell responses for 60 weeks after administration. In preclinical testing, the vaccine protected virus-exposed animals from infection, brain damage, and death.
In addition to developing the GLS-5700 vaccine, earlier this month Inovio and the Wistar Institute received an $8.8 million grant from the Bill and Melinda Gates Foundation to develop a DNA-based monoclonal antibody (dMAb) designed to provide rapid protection against Zika virus infection and its debilitating effects. Unlike vaccines, monoclonal antibody-based therapies provide more-immediate protection but do not develop long-term immune memory. An ideal approach, therefore, would include the coadministration of a dMAb product for immediate protection and a DNA vaccine to train the immune system for longer-term, persistent protection against Zika virus infection, according to Inovio.
As of December 2016, 68 countries and territories (including 48 in the Americas) have reported continuing mosquito-borne transmission of the Zika virus. Unlike other flaviviruses, Zika can be sexually transmitted.
The most common manifestations of symptomatic Zika virus infection include fever, rash, joint pain, and conjunctivitis. Zika is strongly associated with birth defects, most notably microcephaly, which arises from infection during pregnancy. Microcephaly is the result of incomplete brain development. It manifests as an abnormally small head and severe mental retardation. In adults, Zika virus infection is also associated with Guillain–Barré syndrome, which causes muscle weakness of the limbs and in severe cases may cause almost total paralysis, including the inability to breathe. Recent reports suggest that the Zika virus may also be associated with other neurological abnormalities and with abnormalities in other systems, including ocular and cardiac.
Currently, there are no vaccines or therapies for the prevention or treatment of Zika virus infection, but the prospect of developing a blockbuster vaccine has attracted the interest of several major drug makers, including Sanofi, GlaxoSmithKline, and Takeda Pharmaceuticals.
Sources: Inovio Pharmaceuticals; December 21, 2016; and Reuters; December 21, 2016.