Two doses of an investigational DNA vaccine protected 17 of 18 rhesus macaques from infection with the Zika virus in a recent study published in Science. In 6 monkeys that received a single injection at a low dose, subprotective levels of neutralizing antibodies were detected that resulted in breakthrough infections.
The vaccine used in the study, which was led by a team at the National Institute of Allergy and Infectious Diseases, encodes the structural proteins premembrane (prM) and envelope (E). These components are sufficient for the release of virus-like subviral particles that are similar to infectious virions. Sequences for prM and E particles were inserted into an expression vector along with additional sequences to improve expression and subviral particle secretion.
Before administering the constructed DNA vaccine to animals, the researchers verified that it could be expressed by mammalian cells with efficient subviral particle release. Later analyses of vaccinated animals allowed them to define a neutralizing antibody titer threshold that would be necessary for full protection.
In addressing concerns of the possibility of enhanced disease if there is incomplete or waning immunity as observed previously in some secondary dengue virus infections, the investigators noted that in the low-dose single-injection group, there were reduced levels of viremia compared with unvaccinated controls and no visible signs of illness or enhancement of replication following viral challenge.
A phase 1 clinical trial of the DNA vaccine is currently recruiting participants and will test a variety of regimens and doses for safety and immunogenicity. Another study, also recently published in Science, evaluated additional vaccine platforms in rhesus monkeys, including a purified, inactivated Zika virus vaccine and purified immunoglobulin from vaccinated monkeys.
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