A New Era in TB Vaccine Development: Gene Editing Offers Hope
Introduction
Tuberculosis (TB) is one of the oldest and most infectious bacterial diseases, dating back more than 9,000 years. In 2022, 10.6 million people contracted TB, with 23% of cases occurring in Africa. Despite its prevalence, the Bacillus Calmette-Guerin (BCG) vaccine, developed over 100 years ago, remains the only vaccine available. It is primarily effective for infants and young children. However, researchers at the University of the Witwatersrand School of Pathology have made a significant breakthrough by gene-editing the BCG to enhance its effectiveness. Microbiologist Bavesh Kana, a lead researcher, explains the science behind this advancement and its potential impact on other vaccines.
How Vaccines Work
Vaccines function by mimicking dangerous infectious agents, prompting the immune system to recognize the vaccine as an “invader” and mount a response without causing illness. Understanding the immune system’s operation helps clarify how vaccines work, as they harness the natural activity of the immune system.
The Immune System
The human gastrointestinal tract contains about 100 trillion bacteria and viruses. The proteins and sugars on the surface of these pathogens, known as pathogen-associated molecular patterns (PAMPs), differ from those in the human body. When the immune system detects these invaders, it initiates a complex chain of events involving various types of white blood cells. B-cells, a kind of white blood cell, produce antibodies that stick to the bacteria’s surface, either killing or disabling them. This process can take several days, by which time the body might contain billions of bacteria. Once activated, the right cells rapidly produce antibodies, eliminating the invaders and enabling recovery. Some antibodies and white blood cells become memory cells, allowing the immune system to respond quickly to future invasions.
Vaccines
Vaccines mimic the immune system by containing weakened or dead bacteria or viruses, or just a few proteins or sugars from their surface. This convinces the immune system that a real invader has entered the body, prompting an immune response without causing illness. Vaccines are engineered to resemble pathogens but are safe, providing immunological memory that helps the body resist or manage future infections.
Modifying the TB Vaccine
Developing TB vaccines is challenging due to the complexity of the bacterium causing the disease and its proficiency at evading the human immune system. Only one vaccine has been developed against TB in the past century. The research team at the University of the Witwatersrand has focused on the cell wall of TB bacteria, which has a small chemical decoration that allows the bacteria to hide an important PAMP, the NOD-1 ligand, from the immune system. Both TB and the live bacteria used in the BCG vaccine can hide the NOD-1 ligand, making them harder to detect.
Using CRISPR, a gene editing technology, the researchers developed a modified version of the BCG bacterium that cannot hide its NOD-1 ligand. Mice vaccinated with this modified BCG vaccine were able to control TB growth in their lungs compared to those who received the original vaccine. Further studies are needed to modify the vaccine for human use.
Modifying the TB Vaccine
This research presents a promising new vaccine against tuberculosis. With several novel vaccine candidates in the pipeline, there is renewed hope for addressing this devastating illness effectively. This work demonstrates the potential of gene editing in vaccine development, which could lead to more effective vaccines for other diseases in the future.
Source: Inputs from various media SourcesÂ
