Biodefense vaccines

Published on October 29, 2009 Reviewed on November 18, 2016   41 min

Other Talks in the Series: Molecular Basis of Bacterial Infection

This is James Nataro, University of Maryland School of Medicine, Center for Vaccine Development. We are going to talk for a few minutes about category A biodefense vaccines. Talk a bit about considerations and development of vaccines, and the status of some of the vaccines that are available or new development. The NIH has defined certain pathogens as what they call Category A threats.
And these agents have been selected on the basis of several criteria. So, all of them first of all would cause very very severe potentially lethal infections, and secondly they can be delivered by highly efficient routes. That is they can be released into the air, or they can be inoculated into food or water. But all of them have a potential for severe, highly lethal infections that can be efficiently disseminated among large portions of the population.
So, a lot of attention has been devoted to determining what is the optimal approach to agents of biological attack. What kind of interventions should we develop that can protect the population against category A threats? And some of them that have been proposed include nonspecific immune potentiation. That is delivering some kind of pharmacologic agent that will stimulate the immune system to the point that it can come back and overcome any infection that the body happens to encounter. A potential problem with this approach is, that there really is no efficient and reliable way to test the efficacy of this kind of agent in a human population or in human subjects. You cannot do volunteer studies and give someone a fully virulent anthrax infection, for example, to test how well and nonspecific immune potentiator is able to assist that patient. You can do the studies in animals, but it be very very difficult to demonstrate that this in fact is a highly effective response. You can prepare and deliver an antibody, this is a passive immunization strategy. So, for example, you could develop in a non-human animal an antibody against protective anthrax antigens or plague antigens, and you could use those antibodies as an adjunct to antibiotics, to help protect an individual who was subject of biological assault. One problem with that is that monoclonal antibodies may not be highly effective because they may be more variety of these antigens within naturally occurring organisms. And a terrorist, in particular one who has some biological sophistication, may have access to strains in a government fire weapons program, may be able to have access to a strain that may circumvent the epitope to which a monoclonal is derived. So, a passive antibody strategy may require multiple different antibodies a highly reactive polyclonal antibodies for example, rather than more of the monoclonals. Antibiotics, obviously the traditional way to combat a bacterial infection is to use a highly effective antibiotic. One of the problems here is that you have to keep in mind that in the context of a biological assault, the infectious dose to which an individual is exposed, may be supranormal or supranatural, that is that the number of organisms, the number of anthrax spores for example, that someone may be exposed to in a biological attack may be far, far greater than anything that anyone would encounter in a natural setting. So, we know for example that antibiotics may be effective in pneumonic plague or potentially in inhalation anthrax but when someone encounters a far, far greater density of the infectious agent than they would ever be exposed to in natural setting, we expect those antibiotics could be defeated. And then lastly of course vaccination is a tried and true means of protecting against infection. In some instances, even post exposure vaccination can be effective, in smallpox for example, but for most of these agents, the incubation period is relatively short. With plague for example, it is much shorter than it is for say smallpox and so vaccinating an individual who has already been exposed to plague for example, will simply not be an effective intervention. And even post release vaccination that is intended to protect individuals who may be secondarily infected, will probably not be highly efficient because of the fact that it takes a longer time to develop an effective immune response after immunization, according to a conventional immunization strategy, that is likely to be feasible on a population basis. And so all of these approaches have some weaknesses and in some cases they are Achille's heel that simply cannot be overcome.