The Frederick National Laboratory for Cancer Research’s Vaccine Pilot Plant, part of the Vaccine Clinical Materials Program (VCMP), is helping researchers produce investigational Zika vaccines for a new round of clinical trials.

The plant has been manufacturing Zika vaccine candidates since 2016, when it responded to a request from the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) to develop a bulk and vialed drug product (DP) for a Phase I trial. Currently, NIAID is preparing Phase IIa and IIb trials on Zika prevention, which call for more vials of the plasmid DNA (pDNA) vaccine.

While NIAID has been primarily responsible for developing the vaccine, VCMP’s has been producing the vaccine’s physical drug substance (DS) and DP. Since 2016, it has completed four DS batches of pDNA vaccine candidate VRC 5283 and two DP batches totaling roughly 10,000 vaccine doses. The first round of DP has already been used in the Phase I and early Phase IIa studies, and the second round will be released in May. Additional clinical material production is planned for 2017 to meet projected enrollment for the upcoming Phase IIb study.

Making the pDNA vaccine DS takes about five days in a dedicated bacterial fermentation suite. During the first two days, the Zika pDNA is produced via a temperature-induced bacterial fermentation process at 100 liters. Then it spends three days in purification, during which time its cells are lysed and the pDNA product is separated, concentrated, filtered, and frozen. The result of the VCMP’s efforts is 20 grams of DS.

The plant also produces vialed DP from the DS. When the time comes, the DS gets thawed, formulated, and filtered into vials, which takes another two to three days. All DS and DP is scrutinized during a rigorous quality control and quality assurance process.

But the VCMP has done more than just manufacture the vaccine—it has been instrumental in generating and qualifying the stable, transformed Zika bacterial cell line necessary for the routine manufacture. The pilot plant staff also vialed and tested the phosphate-buffered saline placebo used in the studies. The facility’s support of this study was made possible by its earlier contributions to vaccine science, which date back more than a decade.

“The manufacture by the pilot plant leverages platform fermentation and purification technology developed at the pilot plant going back to facility start up in 2006,” said David Lindsay, Ph.D., director, VCMP.

The VRC plans to continue the Phase I trial alongside the planned Phase II trials, although Phase I is already producing promising results—the vaccine has successfully triggered antibody responses against Zika antigens.

If the successes continue, Phases IIa and IIb—collaborative efforts between the VRC and Leidos Biomedical Research, Inc.’s Clinical Monitoring Research Program—should yield even more information about Zika prevention. Phase IIa, a short-term trial, seeks to improve the immune response by determining the most effective injection sites and dosages. Phase IIb will be more long-term and will test the vaccine in areas with high Zika risk, including Brazil, Central America, and the southern United States. Its purpose is to evaluate the vaccine’s effectiveness in people who are naturally exposed to the disease.

While the VRC hopes to conclude the trials by 2019, the VCMP plans to continue producing the investigational vaccine for as long as there is clinical demand for it.

By Samuel Lopez, Staff Writer; photo by Richard Frederickson, Staff Photographer