ATLANTA — New influenza vaccine development is evolving rapidly, with approximately 75 different technologies currently in various stages, said Rick Bright, Ph.D., scientific director for the influenza vaccine project at Program for Appropriate Technology in Health, a global nonprofit health group.
They are desperately needed: Current seasonal vaccines are only 30%-50% effective in older adults, and candidate vaccines for pandemics “are poorly immunogenic in clinical studies,” he said.
Current vaccines may be safe and immunogenic, but they are highly vulnerable to antigenic drift and shift, which compromise efficacy and require reformulation and repeated immunization. Vaccine development is costly, complicated, and time consuming. As the H1N1 influenza outbreak demonstrates, the conventional production process is poorly equipped to respond to a pandemic, Dr. Bright said.
He discussed three promising types of influenza vaccines, each of which holds promise, he said. But all involve significant challenges such as safety, immunogenicity, scalability, and regulatory issues:
LAIV: Innovative Yet Decades Old
Live attenuated influenza viruses have been used to combat seasonal influenza for decades in some parts of the world, but Dr. Bright nevertheless characterized them as innovative. They have yet to be widely accepted or distributed, despite a strong safety record and low cost. It's easy to produce and purify; it has a broad immune response, including some mucosal and cellular immunity; and it is efficacious in naive populations, he said.
There are challenges, however. LAIV “doesn't follow the known, established correlates of immunity,” which can lead to regulatory and licensing hurdles. LAIVs are less effective in nonnaive adults, and there are current limitations on their use in children and some high-risk groups. But some of those limitations are based on “unfounded fears of the risk of reassortment,” he said.
Over the last few years, LAIV technology has expanded into development of both seasonal and pandemic vaccines.
VLP: Dealing With Vectors
Recombinant viruslike particles vaccines, with many varieties in early-stage development, show promise of being both low cost and high yield, with a rapid (12-week) production cycle, he said. Although VLPs contain multiple influenza proteins to resemble virions, they contain no genetic material, and therefore they do not replicate or cause infection.
Animal and early clinical studies suggest a broad immune response, but low immunogenicity may be an issue, he said; VLPs may need adjuvants.
Safety is an issue because all VLPs “rely on some sort of vector.” The challenge is to remove, or demonstrate the safety of, the residual vectors, Dr. Bright said.
Plant-Based: Speedy Development
Plant-based vaccines have been advancing steadily since 2000. They can be produced very rapidly, at about 8 weeks from sequencing to release. New approaches to plant-based expression create high yields with low production costs. Moreover, he said, the approach is “suitable for mixing and matching constantly emerging strains.”
Safety is less of a concern than it is for VLPs because plant-based vaccines are free of animal cells, microbial pathogens, and animal viruses. “It's all in plants, so that implies a safe host cell system.”
Dr. Bright disclosed financial ties with Novavax Inc.
The conventional production process is poorly equipped to respond to a pandemic.
Source DR. BRIGHT