Readers may have noticed that a re-vamped “Ask a Scienceblogger” has appeared, with prior questions and responses at Cognitive Daily and Thoughts from Kansas. Aetiology gets the current installment, discussing the question, “Why is it possible to create vaccines for some microbes and not others?”
First, let me start off with a quibble about how this question was phrased, which suggests that it isn’t possible to create a vaccine for some organisms. This suggests a pessimistic view not shared by researchers in the field. Just because we’ve not been able to create them up to this point–or more pointedly, to create successful ones with the potential for human use–doesn’t mean that we’re down and out. It just means that we have to come up with new targets, new technologies, and even potentially new ways of getting them tested and out into the field.
With that said, there are a number of reasons why we’ve not yet created successful vaccines yet, even against some pathogens that cause a great amount of morbidity and mortality (including the big three: M. tuberculosis, which cause tuberculosis, Plasmodium species, which cause malaria, and HIV):
1) Lack of knowledge about the pathogen and/or host immune response
This is the most basic reason we don’t have effective vaccines against some agents–we’re simply still learning about them, and don’t have enough information to rationally design an effective vaccine. With HIV, for example, we’re dealing with a virus that is highly variable, and can even hide out within the genome for periods of time. We know that the presence of antibody–which blocks or reduces infection with many viruses and bacteria, limiting their ability to result in development of clinical disease–alone isn’t enough to put the brakes on HIV. Therefore, alternative strategies, which are less proven and not thoroughly tested, need to be employed.
For other pathogens, we may not have good candidate antigens (proteins or other molecules that induce an immune response, which often includes production of antibodies, in the host) to use as vaccines, or alternatively, the ones we do have may be highly variable and thus more difficult when it comes to vaccine formulation. Additionally, the antigens expressed by a pathogen may change from year to year (as is the case with the influenza virus), making long-term protection from vaccines elusive for the time being.
How do we know if a potential vaccine works? When researching a vaccine, scientists try to answer this in a number of ways. One way is to use an animal model of disease: give the animal the vaccine, and then challenge them later with the pathogen to see if the vaccine is successful in preventing disease. However, good animal models don’t exist for every disease out there, and even when they do, a good reaction in an animal isn’t a guarantee for the same reaction in the human population.
If the candidate vaccine makes it to human trials, these are done in four phases to first examine safety of the potential vaccine, and then to determine its effectiveness. These are quite time-consuming and expensive, which leads us to the next issue:
3) Time and money, or lack thereof
It takes an enormous amount of time and money to take a potential vaccine from the earliest stages in the laboratory into the human population at large–in the range of $600 million to a billion dollars for each new vaccine. While some vaccine research is funded by the government, much of it is carried out by private companies, who understandably want a return on their investment. Therefore, some types of diseases are prioritized over others (those which are important in developed vs. developing countries, for example). In addition to the cost of research and manufacturing, one must also add in distribution and delivery of the final vaccine, as well as the ever-present risk of lawsuits associated with receipt of the vaccine. Vaccines can be a gamble, and the payoff isn’t guaranteed to be large, making some companies reluctant to invest resources in this area.
Though vaccination has been recognized as one of the ten greatest public health achievements of the 20th century, the creation of novel vaccines is more difficult today than it ever has been. Vaccines are put through more hurdles to assure safety today than they were even 20 or 30 years ago. We have lost our best preservative, thimerosal, due to unsubstantiated links to autism and other conditions–forcing a move away from multidose vials of vaccine to single-use vials, which in turn has driven up the cost of each vaccine dose (a major barrier in developing countries). The obstacles that come with creating a new vaccine are significant, but not insurmountable. New vaccines, however, likely will take more creative thinking and funding than have those of the past.