Almost a century ago, French scientists discovered the world's only tuberculosis (TB) vaccine. Now the World Health Organization warns that without a new one, the world will not win the fight against TB.
A new plan, launched in Johannesburg, South Africa, on 20 March ahead of World TB Day, outlines the gaps and needs in five main areas of TB vaccine research and development: Innovation in research and discovery; better understanding of TB immunity; clinical trials; TB vaccine candidate selection; and advocacy and resource mobilization.
The eight-page plan, or blueprint, and related commentaries have been published in the March 2012 edition of the medical journal, Tuberculosis.
According to Michael Brennan, senior adviser for global affairs at the TB vaccine research and development NGO Aeras, this is the second such plan to be developed by a global consortium of TB partners, and was spurred by massive developments in the vaccine field over the last decade.
Ten years ago, there were no potential TB vaccines in clinical trials. Today - and more than US$600 million dollars later - there are 12 TB vaccine candidates.
"If these new vaccines were successful, we need to be prepared to design the multi-country phase-three clinical trials to get these vaccines marketed and distributed globally," he told IRIN/PlusNews. "If these failed, we need to be prepared with the next generation of vaccines in the pipeline using novel technologies."
Among the major issues highlighted in the blueprint are the need to better understand why some people develop active TB and others do not; develop appropriate clinical trials for HIV patients and those with drug resistant TB; and the need for resource mobilization.
According to Brennan, the large, advanced-stage clinical trials needed to show a TB vaccine's efficacy and safety prior to regulatory approval could cost up to US$200 million. In 2010, only about US$80 million was going towards vaccine research and development, according to the latest survey by the New York-based Treatment Action Group.
Thinking globally, acting locally
Globally, there are about nine million new TB cases annually and 1.4 million people lose their lives to active TB each year. In South Africa, TB - driven by high HIV prevalence rates - is now the leading cause of natural death. Although many people carry TB, only 10 percent will ever develop the active disease. However, people with compromised immune systems, such as those living with HIV or diabetes, are up to 40 times more likely to develop active TB.
In the new National Strategic Plan (NSP) for HIV and AIDS, sexually transmitted infections and TB 2012-2016, the country has prioritized the need for innovative research into new TB drugs, diagnostics and vaccine development, which the government is currently funding. Should a new, effective TB vaccine be discovered, South Africa's NSP also calls for the use of novel licensing mechanisms to facilitate rapid uptake.
"In our country alone, a vaccine could save hundreds of thousands of lives each year and could be instrumental in ultimately eliminating TB as a public health emergency," said South African Health Minister Aaron Motsoaledi in a statement.
"Governments have an important role to plan and, guided by this common strategy, we will do our part to make a vaccine a reality."
This week, South African researchers and policymakers will meet in Johannesburg to set - and cost - HIV and TB research priorities that will ultimately be presented to the South African National AIDS Council and government, according to Gavin Churchyard, chief executive officer of the South African health research institute, Aurum.
In 2010, South Africa made history by becoming the first government to join a patent pool. As a member of the pool established by pharmaceutical company GlaxoKlineSmith's (GKS), South African TB researchers have access to more than 2,300 existing patents and related knowledge on neglected diseases like TB.
Due to the country's high TB burden, and regulatory and research capacity, half of all TB vaccine trials are being conducted in South Africa, according to South African TB Vaccine Initiative (SATVI) researcher Hassan Mahomed.
TB vaccine study
Mahomed is currently part of a clinical trial testing a TB vaccine in infants. With findings expected in 2013, this study will be the first to show the efficacy of a TB vaccine since the French scientists Albert Calmette and Camille Guérin developed the world's only current TB vaccine. Bacillus Calmette-Guérin, more commonly known by its acronym as the BCG vaccine, is widely given to HIV-negative infants in developing countries. However its protective effect wanes in adolescence and adulthood.
TB vaccines have to be tested in countries with high TB burdens, like those in sub-Saharan Africa and Southeast Asia, to show that they work. Mahomed said it was important to ensure that these communities would also reap the benefits of a successful trial.
"Many trials are done in developing countries. Should there be a successful vaccine, this should be made available to the countries that need it most at affordable rates," he told IRIN/PlusNews. "With whatever [vaccine] manufacturer we deal with, we try to ensure that kind of agreement."
The South African government has warned that it will fiercely protect the affordability of any successful TB vaccines that may come out of clinical trial testing within its borders.
"These efforts have been basically done through a non-profit platform... It would be very sad that after a success, that non-profit platform was replaced with a different platform that is profit-driven," said David Mametja, chief director of TB control and management for the South African Department of Health. "Hopefully we don't have the same issues as we had with antiretrovirals. We will jealously guard against any excessive cost that will be linked to making these vaccines available."
South Africa has been battling patents on some second and third line antiretrovirals for years. Still under patent protection and with no generics available, the cost of these regimens have kept them out of the public sector.