Robert Hood / Fred Hutch News Service
When Fred Hutchinson Cancer Research Center immunologist Dr. Erica Andersen-Nissen moved to Cape Town, South Africa, in 2013 her goal was to set up a state-of-the-art laboratory for the Fred Hutch-based HIV Vaccine Trials Network in time to anchor two groundbreaking clinical trials.
Both trials launched last year, and the lab and its 15 researchers, technicians and data manager were ready. The lab has begun analyzing the first of tens of thousands of blood and tissue samples to study trial participants’ immune reactions over the next four years.
As if opening one of the most advanced laboratories in Africa to work on two major clinical trials at the same time weren’t ambitious enough, Andersen-Nissen also is on her way to fulfilling the lab’s long-term mission: Working with local researchers to build scientific capacity in South Africa and its neighboring countries that will extend beyond the work of the HVTN.
“There’s a long history of doing clinical trials in developing countries and taking the specimens out of the country,” Andersen-Nissen said in an interview in her Cape Town office. “Then the people who participate in these trials have no stake in the intellectual property and in the advances that are being made. There’s a growing cadre of top quality researchers in South Africa who should be studying specimens from their own population.”
Twelve of the 14 people Andersen-Nissen has hired are South African, and two others are from neighboring countries.
This is a story of building that lab, from the people up.
Robert Hood / Fred Hutch News Service
‘The opportunity of a lifetime’
Visit the gleaming, 10,000-square-foot Cape Town HVTN Immunology Laboratory today, and it’s easy to think you’re on Fred Hutch’s Seattle campus, from the reception area’s green-and-blue-branded color scheme to the Amazon cloud-computing center next door.
That was not what Andersen-Nissen saw when she first arrived in South Africa four years ago with her family. The lab itself, in a multiuse development with breathtaking views of Cape Town’s iconic Table Mountain, was still under construction. Her first job as lab director was mastering the vocabulary of electricians and engineers, shoving cytometers through doorways and pushing freezers into place.
Working with Dr. Britta Flach, the sole other employee at the time, she set up the lab to meet international “good laboratory practice” standards. Then came the painstaking task of coordinating with the HVTN’s mother lab back at Fred Hutch to ensure that the assays, or tests, that the HVTN has developed to study immune responses in blood and tissue samples produced uniform results whether in Seattle or Cape Town.
“The assays that we’re doing are complicated enough in one lab, let alone coordinating with two labs,” Andersen-Nissen said. “We work to make it standard. Because we’re working with these incredibly precious samples, we have to be really careful to be precise.”
At the beginning, it was all that she could do to get home in time to kiss her children, Julien and Claire, now 8 and 5, good night. Thankfully, her husband, Tom Nowak, a science teacher at an independent school, shares both the children’s schedule and his wife’s love of adventure.
Andersen-Nissen established her globetrotting credentials early, via high school in France and a college semester in Tanzania. But it was teaching biology in Botswana after college that helped set her on her life’s path. It was 1999, and HIV was rampaging across sub-Saharan Africa, with treatment not yet available outside developed countries. The stigma surrounding the disease stymied Andersen-Nissen’s efforts to even teach about the virus in her classes.
By the time she began working on her doctorate — studying the innate immune response under Dr. Alan Aderem at the University of Washington — she knew she wanted to tie her work in the lab to global needs. When it came time to do her postdoctoral training, Aderem introduced her to Dr. Julie McElrath, director of Fred Hutch’s Vaccine and Infectious Disease Program and head of the laboratory program for the HVTN.
Andersen-Nissen had moved from postdoc to staff scientist in the Seattle lab when McElrath offered her a dream job: starting the HVTN’s first lab outside of Seattle from scratch.
“It’s the opportunity of a lifetime,” said Andersen-Nissen, now a senior staff scientist and principal investigator of the Cape Town lab. “I love the intellectual stimulation of the pure science, but if I’m going to spend all this time working on something, I want to help people.”
The lab manager
Robert Hood / Fred Hutch News Service
Dr. One Dintwe, who manages the Cape Town lab and is also an immunologist, had a similar ambition. Dintwe left her home in Botswana for South Africa at 13 to study. Her father worked at a diamond mine, which covered his four children’s educational costs. Her mother, a strong and independent woman who ran a butchery, encouraged Dintwe by word and example.
“She would ask, ‘What do you want to do? How do we make this happen?’” said Dintwe, now 32. “She taught us from a very early age that we need to plan for ourselves.”
Dintwe wanted to become a medical doctor — or so she thought before shadowing some doctors while studying for her undergraduate science degree. South African hospitals, she found, were overwhelmed by trauma victims, men, women and even children suffering from gunshot wounds, stabbings and rape. It was, she said, “a little bit more heartbreaking than I would ever have imagined.” She decided to stick with science.
But the desire to help people remained.
“I was doing microbiology — working on probiotics for ostriches, when I said, ‘Why am I doing this? What is my contribution?’” she said. “So people are going to be eating ostrich steaks, really?’ I just realized I wanted to make a difference. I didn’t want to do science for curiosity any more.”
A friend steered her toward immunology, which she found scientifically fascinating. Her sense of purpose came from applying that knowledge to HIV.
“HIV is personal for me,” she said. “Being from Botswana, we have one of the highest prevalence rates in Africa. I’ve seen at least four family members die from HIV, even when drugs have been available. It’s been the stigma around it, the shame of telling the family.”
Since becoming lab manager, Dintwe longs for more time back at the bench doing experiments. But she has also stepped into the role of mentoring others. When hiring research technicians, she looks for people who share her drive to do more.
“We constantly try to remind them that they’re doing something really important, so people think, ‘I’ve got to give it my best at all times,’” she said. “My mother always wanted me to push myself and do more and be more. I try to do that.”
Robert Hood / Fred Hutch News Service
The research technician
Research technician Saleha Omarjee’s path to the Cape Town lab began with an undergraduate project on the components of blood. A native of Durban, a perpetually sunny South African city on the Indian Ocean, Omarjee became fascinated by hematology and microbiology. She completed a master’s degree in immunology and worked at the university as a research assistant in HIV pathogenesis before moving to the Cape Town lab in July.
Her first job of the day is to make sure the lab’s high-tech equipment is in working order and prep the work space for each day’s experiment, preparing the paperwork and the reagents — the chemical ingredients that go into the experiments, much like the flour and eggs that go into a recipe.
Omarjee does not personally know people with HIV.
“But living in South Africa, we know a big part of the population is affected, even if we don’t know them personally,” she said. “And we know the impact it’s had on children.”
South Africa has the largest number of people living with HIV in the world — almost 7 million people out of a population of about 55 million. (By comparison, an estimated 1.2 million people with HIV live in the United States, population 322 million, according to the Centers for Disease Control and Prevention.) An estimated 360,000 children under age 14 are living with HIV, infected at birth before programs to prevent mother-to-child transmission were in place. Another 2.3 million children have been orphaned because of HIV/AIDS.
Though late to promote the use of antiretroviral drugs, South Africa has made great strides in recent years, reaching 3.4 million people — the largest treatment program of any country. But still, that is only half the people who need it. Meanwhile, more than 1,000 people become infected with HIV every day. Scientists and public health experts see a vaccine as the best hope of controlling and eventually ending the global pandemic.
The stakes give Omarjee a sense of purpose. But the work itself has taught her patience.
“I thought that immediately we would make a big change in the lives of people,” she said. “But this is going to be a long road. I realized I am only working on one small part. I struggled with that at first. Now I’ve accepted that all of this will come together and make a difference eventually.”
Two groundbreaking clinical trials
The long road to an HIV vaccine began in the early 1980s, after the first cases of the then-mysterious illness called AIDS were reported and the virus that caused it identified. Since then, six experimental vaccines advanced to large-scale trials. Of these, just one showed even moderate protection.
A modified version of that vaccine — boosted to be more protective and more durable — is being tested in one of the two major trials now underway. Called HVTN 702, it will enroll 5,400 HIV-negative men and women across South Africa to receive either the experimental vaccine regimen or a placebo. If the regimen being tested achieves at least 50 percent protection, it could become the first licensed HIV vaccine. Results are expected in late 2020.
The other trial, called the AMP study, will enroll 1,500 HIV-negative women in South Africa and six other African countries to study for the first time whether directly infusing a kind of super antibody can prevent HIV infection and eventually lead to an even better vaccine.
Developing a vaccine against a rapidly mutating virus that attacks the very immune cells the body uses to initiate a response has been “a huge challenge,” said Andersen-Nissen. “But it’s also teaching us a huge amount about the immune system.”
The in-depth analysis of blood and tissue samples from both trials underway in the Seattle and Cape Town labs allows scientists to compare the experimental product’s effect on trial participants’ immune systems compared to a control group. They are also able to better understand the role of different immune components such as T cells and antibodies, study how the immune system responds to different vaccine vectors and additives and examine the host-pathogen relationship after infection.
Before the Cape Town lab opened, samples from earlier HVTN trials were stored on dry ice or liquid nitrogen and flown back to Seattle, a labor-intensive and costly process that risked damaging or losing precious specimens. Analyzing the blood samples in South Africa is more efficient. Plus, a local lab makes it possible to analyze mucosal and whole-blood samples, which can’t be frozen.
‘We’ve become full partners’
In addition to these practical advantages, the lab has symbolic importance, both for those donating the specimens and those studying them.
“It gives some assurances for people,” said the Rev. David Galetta, the chair of the community advisory board for the Desmond Tutu HIV Foundation in Cape Town, which participates in the HVTN trials. “Some of the people are skeptical of other countries. You think about shipping your blood out of the country, and you think why? Why not here?”
“It matters a lot to Africans that some of the science is being done on our shores and on our continent,” said Bekker, deputy director of the Desmond Tutu HIV Centre at the University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation. “There’s a sense of pride that we’re not shipping everything off the shores, that our own technologists and people trained in this country are contributing to the science. That we’re able to do the process from designing [the trials] all the way through to finishing the assays and disseminating the results is a testimony to what Africa can do. It means we’ve become full partners.”
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Fred Hutch News Service writer Mary Engel and photographer Robert Hood were in Durban and Cape Town, South Africa, where this story was reported, for the 21st International AIDS conference, AIDS2016.
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