Escherichia coli, or E. coli, is a bacterium found in the intestines of healthy people and animals. While most E. coli strains are harmless and part of a normal gut microbiome, certain strains are pathogenic, meaning they can cause illness. These pathogenic varieties are responsible for a range of diseases, making the development of effective vaccines a public health priority to prevent widespread outbreaks.
The Challenge of a Universal Vaccine
Creating a single vaccine to protect against all forms of pathogenic E. coli is a scientific challenge due to the bacterium’s genetic diversity. Pathogenic E. coli are classified into different groups called pathotypes, each causing distinct diseases through unique mechanisms. This diversity means that a vaccine designed for one pathotype may not be effective against another, as their surface molecules, or antigens, differ.
The main pathotypes relevant to vaccine development are Enterotoxigenic E. coli (ETEC), Uropathogenic E. coli (UPEC), and Shiga toxin-producing E. coli (STEC). ETEC is a primary cause of diarrheal disease, particularly in developing countries and among travelers. UPEC is the leading cause of urinary tract infections (UTIs), while STEC is responsible for severe foodborne illnesses. This requires targeted vaccine strategies for each group.
Targeting Traveler’s Diarrhea
Enterotoxigenic E. coli (ETEC) is the leading bacterial cause of traveler’s diarrhea, affecting millions of international travelers annually. It is also a significant cause of diarrheal illness and mortality in young children in low- and middle-income countries. The goal of an ETEC vaccine is to protect these populations, including military personnel deployed to endemic areas.
Vaccine development for ETEC has focused on targeting the toxins the bacteria produce and the factors they use to attach to intestinal cells. An existing vaccine for cholera offers some limited, short-term protection against ETEC because one of its components is similar to an ETEC toxin. However, its effectiveness is not sufficient for widespread recommendation.
Newer technologies are being explored to improve vaccine delivery and effectiveness. One approach is a skin patch vaccine, currently undergoing clinical trials, which delivers antigens through the skin to stimulate an immune response without an injection. Other strategies involve creating oral vaccines that use inactivated ETEC cells to generate immunity in the gut, where the infection occurs.
Developing Vaccines for Urinary Tract Infections
Uropathogenic E. coli (UPEC) is responsible for the vast majority of urinary tract infections (UTIs). For individuals who suffer from recurrent UTIs, the cycle of repeated infections and antibiotic treatments can be debilitating. A vaccine against UPEC could break this cycle and reduce the increasing problem of antibiotic resistance among these bacteria.
The scientific approach to a UPEC vaccine centers on preventing the bacteria from adhering to the lining of the bladder, an important step in establishing an infection. Researchers have identified proteins on the surface of UPEC that allow the bacteria to attach to host cells. By creating a vaccine that prompts the immune system to produce antibodies against these adhesion molecules, the bacteria can be blocked from gaining a foothold.
Several UPEC vaccine candidates are in various stages of research and clinical trials. A vaccine known as Uro-Vaxom, which consists of extracts from 18 UPEC strains, is available in some European countries as an oral tablet to prevent recurrent UTIs. Another approach being tested is a sublingual spray vaccine called MV140, which has shown promise in clinical trials by inducing a broad immune response.
Vaccinating Animals to Protect Humans
An indirect strategy for protecting public health involves vaccinating animals, particularly cattle, against Shiga toxin-producing E. coli (STEC). This pathotype, which includes the well-known O157:H7 strain, lives harmlessly in the intestines of cattle and other ruminants. While the bacteria do not cause disease in these animals, they can be shed in their feces, contaminating the environment, water, and the human food supply.
In humans, STEC infection can lead to severe foodborne illness, including bloody diarrhea and a complication called hemolytic uremic syndrome (HUS), which can cause kidney failure. By vaccinating cattle, the goal is to reduce the amount of STEC bacteria they carry and shed. This pre-harvest intervention lowers the risk of meat becoming contaminated during processing and reduces the chances of bacteria spreading to crops.
Several veterinary vaccines against STEC O157:H7 have been developed and have received regulatory approval in the United States and Canada. These vaccines work by stimulating an immune response in the cattle that makes their gut environment less hospitable for the bacteria to colonize. Widespread adoption of these vaccines has been limited by economic factors, but they represent an effective tool for reducing the incidence of human STEC infections at their source.