Collaboration Targets Single-Shot Japanese Encephalitis Vaccine

OctoPlus (Leiden, The Netherlands) and SingVax Pte Ltd. (Singapore) have agreed to collaborate to develop a single-shot vaccine for Japanese encephalitis (JE). Most JE vaccines now on the market require multiple injections. The new vaccine will be developed using OctoPlus’s controlled-release drug delivery technology and the “PER.C6” technology licensed by SingVax from the Dutch company Crucell (Leiden, The Netherlands) for manufacturing the inactivated JE virus particles.

OctoPlus has several proprietary controlled-release drug-delivery technologies. For the JE vaccine, the company expects to focus on its modified-dextran system, in which the active ingredient or antigen is encapsulated inside biodegradable microspheres made of modified dextrans (see Figure 1). The crosslinks within the microsphere network are ester bonds that hydrolyze under physiological conditions (37° C and 7.4 pH), causing the microsphere to degrade and release the antigen. The release profile, which can be zero-order or pulsed at a preset time, can be controlled by varying the microspheres’ water content and the number of crosslinkable side chains.

“The ultimate goal is to have at least the same level of immune protection from a single-shot product as you would have from a multiple shot vaccine,” says Gerben Moolhuizen, product director for OctoPlus.

According to Moolhuizen, one of the advantages of OctoPlus’s technology lies in its manufacturing method. OctoPlus encapsulates the antigen in the microspheres using a double (water-in-water) emulsion, without organic solvents. No physical linkage occurs between the antigen and the microspheres, and the antigen remains intact. “We have one of the few technologies that releases these antigens in fully functional form,” says Moolhuizen. “That is a big difference compared to many other systems that are available.”

Under the agreement, SingVax will be responsible for manufacturing the JE virus in Crucell’s PER.C6 human cell line. Using PERC.6 would avoid the purification challenges and concerns about potential protein carryover that have been associated with the mouse-brain–derived vaccine, currently the only JE vaccine available internationally. “There’s been a very big push to get out of mouse brains and into proper cell lines that are well characterized,” says Douglas Thomson, CEO of SingVax. “We believe PER.C6 is a well-tried cell line, and the whole viral particle is a well-accepted antigen for Japanese encephalitis,” he says, noting that these factors influenced the decision to work on JE. “We certainly see a clear path through to get this product at least into the clinic and, hopefully, commercialization.”

JE is a mosquito-borne arbovirus endemic in various parts of Asia. According to the World Health Organization, the disease is severely under-reported, with approximately 50,000 reported cases each year and 15,000 fatalities. SingVax estimates the market potential for a new JE vaccine at US $250 million, with substantial unaddressed opportunities in Japan, Singapore, Thailand, and Malaysia.

Figure 1. OctoPlus’s controlled-release drug delivery system encapsulates drug or antigen in biodegradable microspheres composed of modified dextrans. (Photocredit: OctoPlus)

–Laura Bush