In 2015, almost 1 million children worldwide died from it. Available vaccines such as Prevnar 13 and Pneumovax 23 have been cutting into that reign of terror, but they have some gaps and can be expensive covering only a limited proportion of the bacteria that can cause pneumonia, with a single course for a child in the U.S. costing $600.
A new type of vaccine tested in mice and rabbits might pave the way for a human version to fill those gaps at a fraction of the cost.
“It’s all preclinical,” Blaine Pfeifer, a professor at the State University of New York at Buffalo, said. He’s the senior author of a paper on the new vaccine, dubbed LEPS for the moment, published in October in Science Advances. Preclinical means the new vaccine has not yet reached the point where we can study the idea in humans. “This will have to be put through the usual rigors of clinical trials before we can say anything about ultimate effectiveness. It’s good preclinical data, but that’s where it ends.” Still, he said the “ultimate dream” would be eradication of streptococcal pneumonia, and potentially of related diseases like middle ear infection.
The various strains of this type of pneumonia all come from the same species of bacteria, S. pneumoniae, but they vary in key ways. Pfeiffer said it’s almost as if they are wearing 95 different colored shirts—scientifically speaking, their cells are coated with slight variations of polysaccharides, a type of sugar molecule. The currently available vaccines are only capable of recognizing a few of those sugars, or shirt colors—the most comprehensive covers 23 of them. That leaves dozens of types of the bacteria completely unrecognizable by the vaccine.
Those existing vaccines are created by chemically bonding each type of sugar molecule to a protein, an energy-intensive process that makes them expensive to produce and limits how many of the various shirt colors they can target. The new approach, developed by the team at SUNY at Buffalo and at a spin-off company called Abcombi Biosciences, uses a liposomal formulation—essentially, they pack all the various polysaccaharides inside a small fat droplet, avoiding that bonding process entirely. This makes it far cheaper, with more potential for use in parts of the world where it is sorely needed: Charles Jones, the CEO of Abcombi and the first author on the new paper, said that a standard course of one of the available vaccines for a child in the U.S. can cost $600, but thanks to the ease of manufacture with the liposomal formulation he thinks they can produce a comparable course, with more coverage, for $1.
Another problem with pneumonia vaccines is that we can be victims of their success. The basic function of available options is to prevent colonization by the bacteria, meaning they never establish a presence in our bodies at all. By preventing colonization by those few types of bacteria, a vaccine actually allows the other types to replace them (there is some evidence this is already happening)—and we wouldn’t have any protection against those other strains. Think of a mafia movie: The FBI arrests the bosses, but that just means some of their underlings or a rival family will step up and take over.
The new vaccine’s method of production makes it essentially modular: Theoretically, the team could add in all of the types of bacteria and stuff them into the little fat droplet, without a substantial increase in cost. With complete coverage, it would be like arresting the entire collection of criminals all at once, leaving no one there to restart the business—again, if it proves as effective in humans as it is in animals.
“Having a ‘universal’ pneumococcal vaccine would be excellent,” said Caroline Quach, a pediatric infectious diseases expert and associate professor at the University of Montreal who was not involved with the research. She could not comment on the specific basic mechanism in the novel vaccine, but she said that the idea of preventing the replacement problem, where the uncovered strains take over from the targeted strains, could be extremely beneficial in really making a dent in pneumonia.
Not only that, but the new vaccine has a second line of defense as well. Most of the time, S. pneumoniae doesn’t actually cause disease—the bacteria simply hang out toward the back of our throats, and then occasionally break off to other places like the lung and middle ear and start to do some damage. Along with the sugar molecules, the researchers included two other antigens in the new vaccine known as GlpO and PncO. These antigens target certain proteins that only show up on the bacteria when they do become virulent—when they leave the throat and go off to cause trouble. And importantly, all strains have these proteins: The various types may be wearing different colored shirts, but when they cause disease they turn out to all be wearing identical shoes.
So step one was to increase coverage to as many of the strains as possible, and step two is to address the disease itself if any of the bacteria break through that initial line of defense. This combination approach appears to be effective: Injecting the vaccine into mice and rabbits provoked a strong immune response for 72 of the known pneumonia bacterial types.
“The premise behind this study was to try and design a vaccine for the current situation, but also the future,” Pfeifer said. If it works, it may offer a much-needed cheaper option for sub-Saharan Africa and South Asia, where the WHO says the disease is most prevalent.
Jones said that the company is about a year and a half away from beginning the process with the Food and Drug Administration that will lead to human clinical trials. He guessed early-phase trials could begin within two and a half years. “If everything were to be successful, this would be a massive step forward in the eradication of pneumonia and middle ear infection.”