Humans have been very fortunate to have been protected by vaccines for more than two centuries. The path to get from the identification of an infectious disease to have an effective vaccine is complex, to put it mildly. The issues include research and development, testing, procurement of dependable funding, scaleable manufacturing, equitable distribution, assured safety, management of public fears of inoculation, and global political considerations. Covering all these issues is beyond the scope of this article, but I hope to shed some light on some important aspects of vaccinations and present a view of what we might see in the future. First, a glimpse into the history.
Edward Jenner was a country doctor in Gloucestershire, England. He was a generalist, not a specialist. Jenner had a strong interest in natural history and he was very good at observing basic behaviors. Health Affairs, in “The History Of Vaccines And Immunization: Familiar Patterns, New Challenges”, delved into Jenner’s experience in considerable detail. It reported that sometime during the 1770s, Jenner heard a Bristol milkmaid boast, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Years later, Jenner developed a cowpox inoculation hypothesis for smallpox.
Health Affairs described the remarkable scenario about how Jenner performed the world’s first vaccination in 1796. “Taking pus from a cowpox lesion on a milkmaid’s hand, Jenner inoculated an eight-year-old boy, James Phipps. Six weeks later Jenner variolated [inoculated] two sites on Phipps’s arm with smallpox, yet the boy was unaffected by this as well as subsequent exposures.”
Jenner conducted a dozen similar experiments and documented sixteen additional case histories. With no government or publishing subsidies, Jenner published his studies in “Inquiry into the Causes and Effects of the Variolae Vaccine”. Health Attitude said the work, “swiftly became a classic text in the annals of medicine: His assertion “that the cow-pox protects the human constitution from the infection of smallpox” laid the foundation for modern vaccinology”.
As Dr. Anthony Fauci and others predicted, the mortality has gotten worse since we reached the top of the curves. If we all do a good job in hygiene, screening, distancing, and masks, the country will be able to re-open without uncontrollable spikes in cases. The government is pulling out all stops for therapeutic solutions, as Dr. Kuhn of the FDA has described. Testing is ramping up rapidly. The remaining tool needed is a vaccine for Covid-19 and, hopefully, other variations which may follow.
Significant progress is being made by Moderna Therapeutics, CureVac, Inovio Pharmaceuticals, and others. All are going as fast as possible to advance the clinical trials. Nevertheless, the approach they are taking uses biological DNA and RNA as the core ingredients. As advanced as the current development process is, vaccines as we know them have a number of shortcomings. The most visible is they take a long time to develop and manufacture. Potentially more significant is they can become obsolete if and when the virus evolves, which it will. There are already multiple strains, and there will be more. Finally, the immune response the vaccines produce may not be strong enough to be effective.
A totally new approach is under development using synbio. The Bill and Melinda Gates Foundation has put $60 million into coronavirus research including for the synbio effort. Synbio stands for synthetic biology. Synbio is mostly about the design and construction of new biological parts, devices, and systems, and the re-design of existing, natural biological systems. More specific to the issue of the day, synbio may replace the DNA and RNA ingredients mother nature has provided for the development of vaccines with synthetic ingredients. Huge advances in cloud computing, AI, genetic sequencing, and collaborative tools are making timelines possible which were unthinkable in the recent past.
A vaccine made from synthetic ingredients can potentially offer some significant advantages. The big one is scalability. Synbio vaccines could be produced efficiently for millions or even billions of doses. Another advantage is synthetic ingredients do not need to be refrigerated. This would be a huge benefit for places like sub-Saharan Africa.
Synbio vaccines are developed using computer models, not flasks and test tubes. With billions of calculations, a nanoparticle can be designed which has the exact properties desired. The really big breakthrough with synbio is the attachment of viral molecules to the nanoparticle. Neil King at the University of Washington and his synbio colleagues knew there would be another coronavirus epidemic, like the SARS and MERS outbreaks before the current Covid-19 outbreak. King said, “…there will be another one after this,” perhaps from yet another member of this virus family. We need a universal coronavirus vaccine.” One vaccine for all corona viruses. That will be the breakthrough.
Sharon Begley wrote a beautiful article in STAT which explains the synbio efforts underway in much more detail. See To develop a coronavirus vaccine, synthetic biologists try to outdo nature. STAT has great articles about life sciences and the fast-moving business of making medicines.
Dr. Craig Venter, an American biochemist, geneticist, and entrepreneur known for being one of the first to sequence the human genome, is an advocate for a new and innovative digital approach for the development of vaccines. Venter said the current process used for developing the H1N1, otherwise known as swine flu, vaccine took many months and the supply was barely adequate to cover healthcare workers. He said if the H1N1 virus had been as deadly and widespread as some had forecasted, we would have had a very bad situation.
Venter envisions vaccines being developed using synthetic DNA instead of “billions of eggs”. He has written how DNA data about a virus to be protected against can be developed into a digital recipe and emailed to laboratories which could then begin production of the vaccine at facilities all over the world within 12 hours. Venter said a couple of years ago FDA approval was imminent. The Covid-19 crisis has caused an increase in the sense of urgency.
One final thought about the future of vaccinations has to do with syringes, essential for delivering vaccine. I will be the first to admit, I don’t like needles. My wife and daughter, both nurses, think I am a wuss. I am not afraid, I just don’t like the experience. Unfortunately, many people are afraid for themselves or their children and transfer the fear into inaction. The fear jeopardizes their own health and also the public health.
Syringes could become a thing of the past. Scientists at the Hilleman Labs in India have developed micro-patches which can be used for routine immunizations. The patches are cheap to produce and easy to store without chilling. The patches don’t need special training to be applied, and potentially will be able to be used by consumers at home. Delivered by drones, the patches could become a potential lifeline for rural and poor families around the world. Vaccination by patches could become a reality before the end of the decade.