Lewis Schrager :
Developing vaccines for tuberculosis represents a major global health priority and has been recognized as a critically important strategy to meet the World Health Organization’s ambitious goal of eliminating TB as a global health threat by 2035.
For those living in the developed world, it is easy to overlook the terrible health and economic burden that tuberculosis still places on developing countries.
Even in the beautiful, vibrant, modern city of Shanghai – which played host to the TB vaccine researchers, clinicians and advocates who attended late April’s fourth Global Forum on TB Vaccines – the crushing weight of tuberculosis was brought home to those forum participants who visited the tuberculosis wards of the Shanghai Pulmonary Hospital. Here, three floors of four-bed ward rooms were full of patients receiving treatment for tuberculosis, their faces masked as they lay on their beds, surrounded by concerned wives and husbands, children, and in the cases of the younger patients, mothers and fathers. Such concern was amplified on the sixth floor, reserved for patients with multiple drug-resistant and extensively drug-resistant TB, which can cost 100 times or more to treat than drug-sensitive TB and can take years to achieve cure – if cure, in fact, can be achieved at all. Witnessing these patients quickly brought home to all who made this visit the desperate need for a vaccine capable of preventing TB disease.
In some ways, the challenge of developing new TB vaccines seems as big as the enormous city in which the fourth TB vaccines global forum was held. While major advances toward a vaccine or vaccines capable of preventing tuberculosis have proven elusive, the TB vaccine research and development community has made important gains since the third global forum in Cape Town, South Africa, in 2013, gains that are moving the field closer to reaching the ultimate goal of developing new vaccines for TB.
One major theme of the fourth global forum was the extensive and ever-increasing degree of international collaboration in the drive to develop new TB vaccines. It immediately became clear to all of the nearly 300 participants that never before has the commitment to a focused, coordinated, international approach to developing TB vaccines been greater. This recognition of the need for global cooperation, and dedication to implementing this strategy, was further emphasized by key representatives from the global health community, leading Chinese health organizations involved in TB control and the private sector.
An important area of scientific advancement relevant to TB vaccine development discussed at the forum was an increasing appreciation of the complex means by which tuberculosis hijacks the immune cells meant to kill it and uses these cells in a manner reminiscent of the tale of the Trojan horse to stealthily slip past additional layers of immune defenses and gain access to the lungs.
Through a better understanding of these immune evasion mechanisms, researchers hope to develop vaccines that can trigger unique immune responses that tuberculosis has never encountered before and therefore has not evolved the capacity to avoid. This line of research emphasizes the need to expand the types of vaccine candidates currently under development in an effort to diversify the immune responses generated by vaccines against tuberculosis.
A number of strategies to accomplish this goal were discussed at the forum, including the potential for using a novel cytomegalovirus vector to deliver TB antigens in a way that offers the possibility of ongoing immune stimulation resulting in the potential establishment of an active immunological response close to the site of initial infection in the lung, rather than in the more distant regional lymph nodes. While this approach has not yet been tested in humans, animal experiments are encouraging.
Also encouraging were presentations describing a variety of other new TB vaccine candidates, a number of them derived from either actual Mycobacterium tuberculosis organisms with specific genetic mutations implemented to weaken them and make them safe, or from BCG, the only globally licensed TB vaccine (indicated only to prevent severe cases of TB disease in infants and young children), also with specific genetic mutations in place with the intention of improving and broadening the protection that they can provide.
When attempting to design new TB vaccines, it is also important to consider the actual populations in which the vaccines will be used. BCG, in use since 1921, targets infants and young children. A major thrust of new TB vaccine development is focused on preventing TB disease and transmission in adolescents and adults. Additionally, an important epidemiology study presented at the forum noted that in China, where an estimated 980,000 cases of TB and 41,000 TB deaths occur each year, a major contributor to TB infections and cases over the next few decades will be the elderly. This critical piece of information will need to be taken into account as new TB vaccines, and methods to deliver them, are developed.
The fourth Global Forum on TB Vaccines presented both a sense of significant accomplishment in what the TB vaccine development field has learned thus far, and a sobering sense of the daunting challenges still remaining in the efforts to develop new and effective TB vaccines. Through an international commitment to combat this global disease, there seemed little doubt among forum attendees that these challenges would be met.
(Dr. Lewis Schrager is vice president of scientific affairs at Aeras. He oversees and maintains key external relationships focused on research and development, including the regulatory affairs, global affairs, safety and pharmacovigilance and medical writing departments.)
