A promising bioconjugate Vaccine against superbug Klebsiella
Researchers have now produced and tested a promising bioconjugate vaccine against Klebsiella in mice. This is a vaccine that protects against this worrisome superbug i.e, a hypervirulent form of the bacteria Klebsiella pneumoniae. Researchers, Washington University School of Medicine in St. Louis and VaxNewMo, a St. Louis-based startup., have done this by genetically manipulating a harmless form of E. coli.
Klebsiella pneumonia superbug causes a number of variety of infections including the rare but life-threatening liver infections, respiratory tract infections, bloodstream infections, and other infections. Only little is known about how exactly people become infected with these bacteria, and the bacteria are unusually adept at acquiring resistance to the antibiotics. A prototype vaccine against superbug Klebsiella, details of the study which are published online Aug 27 in Proceedings of the National Academy of Sciences, may offer an effective way to protect people against the lethal infection caused by Klebsiella which is hard to prevent and treat generally.
David A. Rosen, MD. Ph.D., an assistant professor of pediatrics and of molecular microbiology at Washington University, said that for a long time, Superbug Klebsiella was primarily an issue in the hospital setting, so even though its drug resistance was a real problem in treating these infections, the impact on the public was limited. Rosen who is also the co-author of the study on novel Vaccine against superbug Klebsiella added that now we’re seeing Klebsiella strains that are virulent enough to cause death and severe disease in healthy people in the community. In the past five years, the resistant bugs and the really virulent superbugs that have begun to merge so we are beginning to see drug-resistant and hypervirulent strains which are the very scary factor to be considered.
The hypervirulent strains of Klebsiella superbug caused tens of thousands of infections in various countries like China, South Korea, and Taiwan last year, and the bacteria is spreading around the world. Almost half of the people infected with hypervirulent, superbug drug-resistant Klebsiella die. There are two types in particular which are known as K1 and K2 that are responsible for 70 percent of these cases.
Rosen, the senior author Christian Harding, Ph.D., a co-founder of VaxNewMo; and the first author Mario Feldman, Ph.D., an associate professor of molecular microbiology at Washington University and one of the co-founders of VaxNewMo; and his colleagues decided to create a vaccine against superbug Klebsiella. The Klebsiella bacterium’s outer surface is coated with sugars so the scientists designed a glycoconjugate vaccine which is composed of these sugars linked to a protein that in turn helps to make the vaccine more effective and efficient. A similar method of modified vaccines has proven highly successful at protecting people against various deadly diseases such as bacterial meningitis and also a kind of pneumonia.
Harding said that the glycoconjugate vaccines are among the most effective vaccine against superbug Klebsiella. But traditionally they have involved a lot of chemical syntheses, which is slow and expensive. Researchers have replaced chemistry with biology by engineering E. coli to do all the synthesis for them.
The research team genetically modified a harmless strain of E. coli, converting the E.coli into tiny biological factories that are capable of churning out the protein and the sugars needed for the vaccine making. Then researchers used another bacterial enzyme to link the proteins as well as the sugars together.
In order to test the vaccine, the scientists gave groups of 20 mice three doses of the vaccine or a placebo at 2-week intervals. Then the team challenged the mice with about fifty bacteria of either the K1 or the K2 strain. The previous studies had already shown that just fifty hypervirulent superbug Klebsiella bacteria are enough to kill a mouse. In contrast to this, it takes about tens of millions of classical Klebsiella bacteria, the kind that affects hospitalized people, to be similarly very lethal.
About 80 percent infected with the K1 type and 30 percent infected with the K2 type died of the mice that received the placebo. In contrast to this, of the vaccinated mice, 80 percent infected with K1 and all of those infected with K2 survived.
Feldman said that they are very happy with how effective this Vaccine against superbug Klebsiella was and they now working on scaling up the production and also optimizing the protocol to take the vaccine into clinical trials soon.
The goal of the study is to get a vaccine ready for human use before the hypervirulent superbug strains start causing disease in even larger numbers of people.
Rosen said that he as a pediatrician wanted to see people get immunity to this bug as early as possible and It is still rare in the US, but given the high likelihood of dying or even having a severely debilitating disease, he thinks one could argue for vaccinating everybody. And soon we will not be left with a choice. The number of cases is increasing, and we are going to get to the point that we will need to vaccinate everybody, he added.