Mix-and-Match Vaccine Platform May Boost Immune Response & Duration
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The Infectious Disease Research Institute (IDRI), a non-profit biotech organization, is working with a newly-formed consortium to develop a next-gen COVID-19 vaccine that will be stable at routine temperatures and that may be able to confer immunity for a longer duration.
“The first-generation vaccines were incredibly important, but they are not sufficient to take us through this pandemic or for the next pandemic,” IDRI CEO Corey Casper, M.D., MPH told BioSpace. Although the currently-authorized vaccines meet the immediate needs of industrialized nations, they fall short when breadth and duration of protection are considered.
“Requiring boosters every six months will mean that a declining proportion of people will be fully protected because compliance with booster shots is always less than with the initial vaccination series. We are one mutation away from having a variant of concern that renders our current vaccines insufficient to protect us,” Casper said.
Currently-authorized vaccines also fail to meet the needs of resource-constrained regions. “So, we’re working on that.” The consortium ImmunityBio formed recently with IDRI, Amyris, Inc., Texas Children’s Hospital Center for Vaccine Development and Baylor College of Medicine “brings together multiple vaccine technologies to advance a heterologous approach that remains uncommon in the pharmaceutical industry,” Casper said.
IDRI’s primary vaccine is RNA-based. Phase I/II trials will begin in the coming months in South Africa. “This can give pancoronavirus protection, and the duration of immunity possibly could last a decade.
“Our RNA technology is different than the technology used by Pfizer and Moderna,” Casper said. The lipid nanoparticles that others use “are like jelly doughnuts,” he said by way of analogy. The payload is being carried through the delivery system inside. Those nanoparticles envelop the RNA in the lipid to protect it from degradation from Ribonuclease (Rnase) and ease its transport into cells
IDRI’s technology, in contrast, “is like a cake doughnut with sprinkles (RNA) on the outside. The nanostructured lipid carrier (NLC) is positively-charged to attract and attach the RNA to its surface. The RNA doesn’t degrade because it is electrostatically bound to the NLC and, therefore cannot be destroyed by RNase. Its lipid core contains an adjuvant that gives it an immune boost.”
One advantage of this approach is that the RNA construct can be determined at the patient’s bedside and adjusted to address the current viral variants of concern. “While the original COVID-19 vaccines were made over months, we can address a new threat in a matter of weeks.”
The other advantage is that the NLC can be stockpiled and maintained for a year under normal refrigerated temperatures, and for several months at room temperature. Addressing new threats can be accomplished by adding new RNA constructs to the surface of the carrier.
That rapid-response capability is particularly beneficial for influenza vaccines, which are designed six months before flu season and based upon predictions of the most likely strains. It also suggests that vaccines for prevalent diseases in a given region – such as yellow fever and Zika – may be combined into one inoculation.
IDRI’s RNA platform develops a self-amplifying, self-adjuvanted RNA vaccine that can be scaled up quickly and that can amplify antigen expression at lower doses than conventional mRNA vaccines. It is based on a modified Alpha virus – specifically, a Venezuelan equine encephalitis virus – in which the virus protein has been removed. Once inside the target cell, it completes 10 replication cycles, thus making it possible to use a lower dose, reduce manufacturing costs and possibly elicit a stronger immune response.
IDRI partnered with ImmunityBio to take a mix and match – a heterologous prime and boost – approach to vaccines, Casper said. For COVID-19, he explained, “Adenovirus vaccines (including the adenovirus 5 vaccine IDRI is developing) create a T cell response, and mRNA vaccines generate neutralizing antibodies. So, when they are given together (or in sequence), you get multiple types of immunity,” and, therefore more robust protection.
The consortium and IDRI are working to develop a nasal spray to further enhance COVID-19 immunity by eliciting both a systemic and a mucosal response. “We are moving to a challenge model to determine whether our vaccine can prevent the virus from replicating in the nose. With COVID-19, vaccinated people can still transmit the virus, and nasal administration might be able to abrogate that. If so, this could be a significant step forward.” The work currently is in mouse models.
The organizations are looking at ways to improve therapeutic vaccines, also. The technology for such vaccines limited their success but, “Promising technologies from companies like ImmunityBio and IDRI may be able to bridge that gap,” Casper said. “ImmunityBio started as a cancer company,” Casper said, “but cancer vaccines have had a rocky road,” because of their ineffective response to tumor antigens.
“Now we are trying a few other things,” he continued. The future of this technology is to target specific antigens in certain tumors using a mix-and-match approach.
IDRI was formed about 30 years ago to fill the gap between academia’s basic research and the biotech industry’s large-scale development and testing. “We evolved by focusing on specific elements of vaccine technology that don’t meet key needs,” Casper said. Typical refrigerator (2-8°C) or room temperature storage is a primary example. Because many impoverished countries lack a pharmaceutical-grade cold chain, life-saving vaccines that are taken for granted in the industrialized world are out of their reach.