While I have written in the past about the need for better vaccine development, I have also argued that trying to develop a perfect vaccine is like trying to climb a mountain that has no summit.
We have made important progress over the last few decades, and that progress is evident when one considers the impact of today’s vaccine regimen. Since the introduction of the first diphtheria, tetanus and pertussis (DTaP) vaccine in 1969, the incidence of diphtheria, tetanus and pertussis has been cut in half. (DTaP was only licensed as a single vaccine when it came to market.)
If someone says the vaccine is working, they are referring to a constant improvement and not any one particular evidence-based improvement. We have really made some progress in certain areas.
But in certain other areas, a much greater focus is needed to be had. In India, for example, infections caused by chickenpox and dengue virus are so severe that children die from those infections. They also fall ill with serious complications from diseases caused by parasite infection. Though both diseases are listed as being among the most commonly prevented by a vaccine, many children in those areas still die.
We have spent a lot of time trying to develop a vaccine for chickenpox and dengue. Neither vaccine has been effective for some time and it seems a priority to explore other approaches to those infections.
It makes sense to try these approaches if we are trying to reduce the number of children dying from infections caused by malaria, whooping cough and tetanus and deaths caused by secondary infections in the neonate and under-fives.
As we move forward in vaccine development, one of the problems we face is finding better combinations of existing vaccines. We know that there are people who could benefit from having no vaccine at all. I realize that making a vaccine for those who could benefit from no vaccine makes less sense than trying to make a vaccine for those who might benefit from a single vaccine.
We have to decide which vaccines we are going to maintain or try to develop some combination of vaccines. It is less easy to determine which vaccines to develop for people in developing countries, because there are fewer children around to get their vaccines.
One major issue facing vaccine researchers is the shortage of the traditional monoclonal antibodies (MAbs) that are responsible for the immune system’s response to a pathogen or vaccine. Lack of MAbs makes it very difficult to identify which vaccines may work best in a particular country.
We now have a new option that will work well for people in developing countries. The first MAbs for dengue and C. dengue were developed at the Center for Biotechnology and Interferon Research (CBIR) at the National Institute of Allergy and Infectious Diseases (NIAID). CBIR developed C. dengue with AZD9291 and dengue with AZD3331 and introduced them in clinical trials in 2015 and this year, respectively. The goal of the trials was to improve the Tdap vaccine, so that parents in low-income areas are no longer required to bring a separate sample to get the vaccine.
ZMapp, a monoclonal antibody designed to provide some protection against Ebola, also originated at CBIR. ZMapp’s effectiveness in treating Ebola in a clinical trial made it one of the top ten pharma breakthroughs for the year.
C. dengue appears to respond to AZD9291 much better than it did to ZMapp, and that may increase the chance that AZD9291 will be approved for use in people in low-income countries.
VAHB is the Center for Vaccine Development, one of 11 discovery centers at NIAID.