Editors’ note: This is the first part of a two-part series on how to tackle the next infectious disease outbreak, from doctors at the Mayo Clinic.
The deadly Ebola virus has now breached the borders of yet another African country, Senegal, with the World Health Organization warning that 20,000 people could eventually be infected as the deadliest outbreak of this disease worsens. As the death toll reaches nearly 2,500, a new study from Oxford University predicts that 15 more countries are at risk of Ebola exposure.
As we watch the daily tally of deaths rise, we need to focus on the consequences for the living: the impact on families, health care systems, countries, and economies.
Franklyn G. Prendergast, M.D., Ph.D, Steven G. Reed, Ph.D. &
Darrick Carter, Ph.D
Franklyn G. Prendergast, M.D., Ph.D, is a member of IDRI's Board of Directors. He is also the
Edmond and Marion Guggenheim Professor of Biochemistry and Molecular Biology and Professor of Molecular Pharmacology and Experimental Therapeutics at the Mayo Medical School.
Steven G. Reed, Ph.D., is the Founder, President & Chief Scientific Officer at IDRI. His research interests have focused on the immunology of intracellular infections and the development of vaccines and diagnostics for infectious diseases. He led the team that, together with GSK, developed the first defined tuberculosis vaccine to advance to clinical trials, as well as a more recent second generation TB vaccine candidate and the first defined vaccines for leishmaniasis, as well as the K39-based diagnostic tests currently licensed for leishmaniasis.
Darrick Carter, Ph.D, is the Vice President of Adjuvant Technology at IDRI. His work centers on new immunomodulatory agents and formulations, as well as the process development necessary to take vaccines and therapeutic candidates from the lab to the clinic.
And Ebola is only one part of the picture. In parallel to Ebola, concerns have been raised in other parts of the world about Middle East Respiratory Syndrome CoronaVirus (MERS-CoV), which has claimed more than 250 lives so far. More than 700 cases of MERS-CoV have been documented in 20 countries, including the United States. Like the SARS virus, which killed nearly 800 people a decade ago, MERS is deadly. Both SARS and MERS are coronaviruses, named for their shapes, and both are thought to have originated in bats and spread through other animals to humans.
Unfortunately, we don’t know where MERS is headed, or how much death will ultimately spread from it. It could eventually fade away on its own, or it could become even more contagious over time. It could also go the way of SARS---a new disease that appeared on the horizon in 2003, spreading quickly and resulting in an estimated 8,000 cases and 750 deaths. While the disease lasted a short time, it had a long-lasting effect, both psychologically and economically. Schools closed, travel advisories were issued, and national economies were affected, with some experts estimating the cost at more than $11 billion.
When there is an outbreak and spread of a disease, the number of deaths may be small but the burden of suffering is enormous. Take chikungunya, for example. An infectious disease carried by mosquitoes, chikungunya isn’t generally lethal, but the pain it brings is horrible and sometimes long-lasting, keeping those infected from contributing to their families or communities. Found in Asia and Africa for decades, chikungunya has become more widespread, arriving in the Caribbean at the end of 2013 and already infecting as many as 250,000. To date, nearly 100 American travelers have brought the disease home.
But the real question is what happens if there’s a widespread emergency outbreak of MERS, chikungunya, or another newly emerging or re-emerging infectious disease---how well positioned and prepared are we for a rapid response? Just a few months ago, the U.S. joined 26 other countries to tackle this issue, citing the need to accelerate progress toward a world that is safe and secure from the threat of infectious disease.
The rapid increase of Ebola and MERS point toward the need to be vigilant, to anticipate, and to prepare for the next outbreak. While we don’t know what or when, we do know one thing: there will be another disease outbreak, posing a threat to both health and economy.
Diseases, which epidemically used to be geographically localized because populations were less mobile, are today’s frequent flyers. Just 150 years ago, it took nearly an entire year to circumnavigate the globe. Today, that feat can be accomplished in a day. The rapidity with which pandemic flu, or smallpox, or even very rare infectious diseases, such as Marburg or Lassa Fever, could potentially spread is daunting. The recent outbreak of Ebola makes us painfully aware of this fact.
The good news in this grim scenario, provided by our latest scientific research studies, is that we can efficiently produce more powerful vaccines that protect a greater number of people than ever before.
Unfortunately, though, the vaccines currently on the market are built on technologies from decades ago; in fact, the technology hasn’t advanced much beyond Jenner’s smallpox vaccine, which employed the now-classic approach of using a whole weakened organism as the vaccine itself.
We know we can do better than these primitive vaccines, which are only effective in certain parts of the population. We can produce vaccines that are more effective in populations that are most vulnerable to infectious diseases: the elderly, whose immune systems have been consumed by a lifetime of combat against infectious intruders, and the very young, whose immune systems are simply too new.
Today’s vaccines have four components: an antigen that provokes an immune response; an adjuvant that boosts the immune response; a formulation (that may include the adjuvant) that presents the mixture in a stable and optimal manner for human injection; and a delivery mechanism: often a needle for injection, but this could be a skin patch or a formulation for ingestion – many people remember taking the polio vaccine via a sugar cube.
By optimizing each of these, we can produce vaccines rapidly and effectively.
Key to next-generation vaccines are adjuvant compounds, which trigger and enhance the immune response in order to boost the vaccine’s effectiveness, versatility and reach.
Adjuvants improve a vaccine’s reach through economical “dose sparing”---reducing the amount of vaccine needed for a dose, thereby reducing the cost of the vaccine per person and increasing the available supply many times over. Additionally, by broadening the immune response to a stockpiled vaccine, adjuvants enable protection against a wider array of related pathogens belonging to the same group, e.g. viral seovars.
The danger of production bottlenecks in case of a pandemic was in evidence in September 2009, when the main wave of the H1N1 swine flu pandemic hit the United States. Vaccine production was delayed by a lower-than-expected yield of vaccine from the chicken eggs in which the vaccine virus is grown. And it wasn't until the end of January 2010 that every U.S. resident who wanted the vaccine could get it. By then, many people either had had the flu already or figured the danger had passed. Six months later, there was only a trickle of H1N1 infections, but deaths and hospitalizations continued among at-risk people who hadn’t been vaccinated.
Our latest research centering on adjuvants in flu vaccines tells us that this situation doesn’t have to be repeated. In terms of dosage, for instance, we found that when adjuvant compounds were used, one shot of flu vaccine could actually do the work of two.
When it came to the amount of flu vaccine needed, the results were equally encouraging. Before, as much as 100 micrograms of vaccine were required per dose for a single person; but when adjuvants were added, just 3.8 micrograms provided comparable levels of protection as measured by the immune response to the vaccine. This dose sparing of vaccine could expand government stockpiles to cover 30 times the population currently targeted.
Adjuvants that broaden the immune response can protect people against other genetically related viruses and new plagues, too---not just the standard, identified viruses. The elderly and the young haven’t always responded well to flu vaccines, but the inclusion of adjuvants in our studies broadened the immune response, and this has the potential to help extend protection to vulnerable populations.
Finally, our research showed that adjuvants are able to accelerate the response to the flu vaccine, as well as others. We think that protection could kick in in a few days, as opposed to the standard three weeks, raising the possibility for a broad array of single dose vaccines.
The bottom line is that, in order to anticipate and deal with a disease outbreak, we need to have components (like adjuvants) at the ready and stockpiled, so that we can rapidly respond to the need for a new vaccine. The recent outbreak of Ebola highlights that this is essential.
We also need to begin to rationally think about delivery systems like microneedles and skin patches that allow people to self-administer vaccine. If there's a disease outbreak, people wouldn’t congregate at hospitals and health care centers where they would get infected or spread illness. Instead, they could just stay home, get their vaccine patch out of the mail and administer the dosage themselves.
