Keiser said WRAIR’s focus on vaccines is multifaceted. They’re currently conducting clinical trials of dengue vaccines, while also working to develop a blood test to determine a vaccine’s effectiveness. “For some infectious diseases you can say, ‘based on this blood test result I know you’re protected from that infection.’ Right now there’s not a good blood test like that for dengue,” he said.
Because there’s no blood test to ascertain the potential dengue vaccine’s effectiveness, Keiser explained that they’re developing a challenge model, where volunteers would be exposed to an attenuated version of a dengue virus in a monitored setting. The process is nearing the volunteer recruitment phase.
“The idea is to give them a very mild and safe infection with dengue fever,” he said. “If we can prove that the model is safe and predictable, we can use that model to test vaccines and antiviral drugs and do all sorts of other studies. We could take 10 volunteers and give them a candidate vaccine and give 10 other volunteers a placebo vaccine. If we give them all this challenge strain, we could quickly get an idea of whether or not this vaccine prevents dengue.”
Keiser said a unique aspect of their institution is that, although they collaborate with industry, they work for the warfighter. “Our motivation is not the short-term economic interest; our motivation is to find a solution.”
Noting that challenge models already exist for influenza and malaria, Keiser characterized a successful challenge model for dengue as a tool that could enable many breakthroughs for vaccines and antiviral drugs.
Keiser said a unique aspect of their institution is that, although they collaborate with industry, they work for the warfighter. “Our motivation is not the short-term economic interest; our motivation is to find a solution.”
Complex circumstances in vaccine development involve factors like how widespread the need is and its financial feasibility. For example, there has not been a civilian need for the adenovirus vaccine, but clearly there is a military need. “When the vaccine is not given, not only do a lot of soldiers who are in basic training miss days of training because they’re ill and have to recycle, but there have actually been deaths reported – not commonly, but it can be a fatal respiratory infection,” Keiser said. “Because there’s no civilian market for an adenovirus vaccine, it ends up falling on the government, really, to support that whole product line.”
In a collaborative effort, Keiser said vaccine manufacturers, under government contract, have made the adenovirus vaccine for defined periods. WRAIR scientists continue efforts to secure an uninterrupted supply of vaccine. But, he added, there are other vaccines that fall into the category of good for the military but not financially feasible for a vaccine manufacturer to make. With chikungunya, for example, the pattern is that epidemics rise and fall in a shorter period than a vaccine can go through development and manufacture. “I mention that as one of the top threats for the warfighter; meanwhile, it may not be a top priority for the industry,” he said.
“That’s not just a scientific problem,” he continued. “It may be more of a financing problem.”
In terms of new advances in viral research, Keiser noted that utilizing genomic sequencing technologies being applied in the antibacterial fight might enable discovery of specific elements that apply to a group of viruses with genetic similarities, enabling vaccine development that targets those shared genetic features. For example, dengue, a Flavivirus, has structural similarities with other Flaviviruses for which vaccines exist, like yellow fever or Japanese encephalitis.
It is a certainty, Keiser concluded, that with increased air travel, expanded range of mosquito vectors, and continued expansion of human activity into underdeveloped areas, the need exists to identify the optimum viral targets and develop vaccines more quickly.