Vaccines: our greatest hope in defeating AIDS, Ebola, TB, and other infectious diseases

The largest and deadliest Ebola outbreak in history, which began in 2014, claimed more than 11,000 lives before finally petering out in 2016.

What is different about this new outbreak, the DRC’s largest to date, is that it is occurring in a conflict zone. That makes identifying and treating Ebola patients extra difficult. Another difference is that we now have a highly effective — though still investigational — Ebola vaccine.

During the 2014-2016 Ebola outbreak, I was working at Merck. My colleagues and I, in partnership with many external collaborators, worked with unprecedented speed and urgency to develop, manufacture, and test an Ebola vaccine candidate that was originally created by scientists at the Public Health Agency of Canada. This vaccine candidate progressed from the first-in-human studies to evidence of vaccine effectiveness in only 10 months — a process that typically takes years. The vaccine was found to be 100 percent effective at preventing infection with Ebola when it was tested in a ring vaccination efficacy trial in Guinea.

The vaccine was not developed in time to have much of an impact on the 2014-2016 outbreak, but it is now being deployed through a compassionate use program in the DRC and Uganda to protect people at highest risk of Ebola infection, including contacts of individuals diagnosed with Ebola and front-line health care workers. The vaccine is one of several strategies being implemented to stymie this latest outbreak.

While the remarkable challenges of trying to control an Ebola outbreak in the midst of instability and violence have frustrated efforts to quash this outbreak, the situation would almost certainly have been worse in the absence of an effective vaccine.

The development of this Ebola vaccine candidate is a remarkable success story. It shows how public and private sectors can collaborate when they have a shared commitment to develop a highly effective and urgently needed vaccine.

We need to foster even more effective multi-sector partnerships to address other established public health threats like HIV and tuberculosis (TB), and to proactively prepare for other infectious disease threats that will emerge in the future.

Although HIV and TB may prove to be more intractable pathogens than the Ebola virus, neither will be defeated without effective vaccines. Fortunately, there is scientific and political momentum building on both fronts.

Despite tremendous strides in providing life-saving treatment to people living with HIV and multiple ways to prevent infection, the virus continues to spread at an alarming rate. Nearly 2 million people were newly infected with HIV last year.

The situation with TB is just as dire, if not more so. Although TB is treatable and even curable, which is not currently the case for HIV, 1.6 million people died last year as a result of TB infection, earning it many notorious distinctions: the most deadly infectious disease, the top killer of people living with HIV/AIDS, and the ninth leading cause of death around the world. Considering that an astonishing 10 million new cases of TB disease were reported last year, the overwhelming need for newer and better TB vaccines becomes brutally apparent.

Recent results from two TB vaccine trials are providing a new level of optimism that it should be possible to protect against this centuries-old pathogen by vaccination. A Phase IIb study involving more than 3,500 adult volunteers from Kenya, South Africa, and Zambia showed that the GSK investigational TB vaccine candidate, known as M72/AS01_E, was 54 percent effective overall at preventing active pulmonary TB disease in adults. Results from another recent clinical trial suggest that revaccinating adolescents with the only licensed TB vaccine, bacilli Calmette-Guérin (developed nearly 100 years ago), might offer another strategy for protecting against TB. This study showed that revaccinating South African adolescents with the same vaccine they received as infants was 45 percent effective in preventing sustained TB infection.

Efforts to develop a widely effective HIV vaccine are now focused on inducing highly specialized antibodies known as broadly neutralizing antibodies that are widely thought to offer the best hopes of protecting against the virus. Because these antibodies, which can potently block infection with diverse HIV variants, aren’t readily made by the immune system — they occur only rarely in response to natural HIV infection — researchers are exploring innovative techniques to try to develop vaccines that could provoke the immune systems of HIV-uninfected people to make them. The International AIDS Vaccine Initiative, which I lead, and its partners recently advanced a vaccine candidate into clinical trials that seeks to do just that. Others in the field are trying additional approaches to reach the same goal.

Researchers working on both HIV and TB vaccines must redouble their efforts to expedite the development of promising candidates and use emerging insights in immunology to hasten the design and development of even better ones. Success will only come from innovative science and creative partnerships between the public and private sectors, much like those that were formed during the 2014-2016 Ebola crisis.

Defeating HIV and TB will ultimately depend on vaccines being affordable and accessible across the globe, particularly in the places where the burden of these diseases remains unacceptably high.

By Mark Feinberg
Mark Feinberg, M.D., is the president and CEO of the International AIDS Vaccine Initiative

Source: STAT