Science policy has been at the forefront of many scientists’ minds lately, with challenges to communicating and implementing recommendations based on experimentally-produced data. At the top of this list is the mainstream acceptance of vaccinations as a safe and effective way to prevent transmission of infectious disease. The American Society for Microbiology and its members strongly support the use of vaccines to benefit both population and individual health. Fortunately, this sentiment was echoed at the recent World Economic Forum in Davos, where the governments of Germany, Norway, and Japan have joined forces with the Wellcome Trust and the Gates Foundation to commit $460 million toward development of vaccines to prevent a deadly outbreak mirroring the 2014-16 Ebola outbreak in West Africa. The investments will be channeled through the newly launched Coalition for Epidemic Preparedness Innovations.
The coalition will first concentrate on emerging infectious diseases in regions of the world with poor infrastructure, where an outbreak can quickly spin out of control. These targets include Lassa virus, Middle Eastern Respiratory Syndrome (MERS)-coronavirus, and Nipah virus. Although these viruses originated in different geographical parts of the world (West Africa, Saudi Arabia, and Bangladesh, respectively) they share an important characteristic: all have animal reservoirs, making eradication nearly impossible and turning vaccination into the best human defense against disease.
There are many effective vaccine types that safely block disease transmission, from killed-microbe (the disease-causing agent can no longer replicate but retains its shape) to attenuated-microbe (the disease-causing agent can replicate but is missing key disease-associated genes) to toxoids (disease-associated toxins rendered inactive). What different vaccine types have in common is the ability to represent a microbial epitope (shape) that the immune system can recognize and react against, building memory in case the disease-causing microbe infects the vaccinated individual.
One of the newest vaccine types is the recombinant vector vaccine. This vaccine type utilizes a harmless microbial vector, such as vesicular stomatitis virus (VSV), that can replicate but cannot cause disease in humans. Part of the vector genome is replaced with that of a disease-causing microbe; for example, by replacing the VSV glycoprotein gene with the Zaire Ebola virus (ZEBOV) glycoprotein gene, scientists were able to make an rVSV-ZEBOV vector. People infected with rVSV-ZEBOV will generate an immune response to the Ebola virus glycoprotein, and this immune response can fight infecting Ebola viruses based on recognition of its glycoprotein. This exact strategy was the one used in the recently celebrated successful Ebola vaccine clinical trial, the first successful recombinant vector both safe and effective, prevent disease in 100 percent of those vaccinated.
What might a vaccine against a yet-to-be-determined microbial strain look like?
Schematic overview of multivalent viral vector vaccine design. Source.
Planning for an outbreak that hasn’t occurred can be difficult, especially if there are multiple circulating serotypes. One approach is to use a similar recombinant strategy with multiple genes are expressed in a single viral vector. This multivalent vector vaccine strategy is the topic of a recent Clinical and Vaccine Immunology review. Using multiple transgenes, a single viral vector can confer protection against multiple strains with a single inoculation (see figure). While this strategy hasn’t been applied to human vaccines yet, one can imagine the benefits from including multiple viral epitopes to protect against all four circulating serotypes of Dengue virus, a disease where infection with one serotype doesn’t protect against reinfection with a different serotype.
This strategy could even be used to confer protection against two different infectious microbes. Combinations of different microbial epitopes on the same viral vector might simplify vaccine strategies, decreasing the number of required inoculations. The ability to protect against multiple diseases in a single vaccination would simplify vaccine administration in areas with reduced access to health care facilities – the very places where emerging infectious diseases such as Lassa fever, Nipah fever, and MERS outbreaks have occurred.
Given an emergency outbreak, the research community acts swiftly to generate candidate vaccines: see the recent Ebola vaccine success story or the 20 Zika vaccines now in various stages of clinical trials. But every candidate vaccine is just that – a candidate – until it has undergone extensive safety and efficacy testing. By preparing, testing, and storing vaccines before an outbreak occurs, public health officials will be better prepared to halt an outbreak, should one occur.
Want to learn more about scientific development of vaccines? At 6pm EST on February 23rd, ASM is hosting a Microbes After Hours session on “The Never-Ending Vaccine Race.” Veteran medical journalist Meredith Wadman will discuss the controversial story of the development of rubella virus vaccine, and NIH Vaccine Research Center scientist Dr. April Killikelly will discuss the latest technologies in vaccine development. You can watch the talks (and pose questions to the speakers) through ASM’s live YouTube stream.
Photo credit: Vaccination image