Vaccine Briefs

After Long Career, Peggy Johnston Retires from Post at NIAID

Peggy Johnston, who served as director of the vaccine research program at the Division of AIDS (DAIDS) at the US National Institute of Allergy and Infectious Diseases (NIAID) for the past 12 years, retired in December after a 30-year career that spanned both the public and private sectors, and in the last 15 years focused almost exclusively on the search for an AIDS vaccine.

Johnston, who just turned 60, joined NIAID in 1987 as a program officer. “I sort of think I grew up at NIAID,” she noted. In 1993, she was named deputy director of DAIDS. She left three years later to become IAVI’s founding scientific director and first senior vice president for scientific affairs. Johnston returned to NIAID in 1998 to serve as director of the DAIDS Vaccine and Prevention Research Program (now the Vaccine Research Program), managing a US$351 million research portfolio by 2010.

Johnston helped see through the 16,000-person RV144 trial in Thailand that was launched under a cloud of controversy, but ultimately showed the first evidence of vaccine-induced protection against HIV (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009).

The results of the RV144 trial represented an emotional high for the normally stoic Johnston, who uncharacteristically teared up when the results were first shared with investigators in 2009. Two years later, the field is forging ahead with an array of post-RV144 studies, in addition to pursuing other promising avenues of research, but Johnston says she doesn’t feel the need to stay. “I’ve never been the kind of person who had to be there at the end,” she says. Johnston believes the goal of developing an AIDS vaccine is reachable. “I’m thinking we’ll get there and I’ll be alive to witness it.”

Nelson Michael, director of the US Military HIV Research Program, one of the collaborators of the RV144 trial, said there were major operational issues with launching the study, and as a result it took twice as long to enroll participants in the trial. “Peggy was a rock during those times,” Michael recalls. “It was really important to have someone with her gravitas, and my respect for her, which was always high, grew enormously. We were kind of in the foxhole together.”

While she has left her current position, Johnston will still be assisting NIAID in the restructuring of its HIV/AIDS clinical trials networks and lives in Washington, D.C., with her partner. —Regina McEnery

New Commitments from Public and Private Sectors to Try to Eradicate Polio

Efforts to eradicate polio got a much needed boost last month when government and private donors announced commitments totaling nearly US$200 million to supply and deliver polio vaccines in a handful of countries where the disease is still endemic and to support disease surveillance.

UK Prime Minister David Cameron said his country intends to provide $61 million to the Geneva-based Global Polio Eradication Initiative—roughly doubling the UK’s 2010 commitment. The Bill & Melinda Gates Foundation, which has already spent $1.28 billion on polio eradication efforts, also announced that they will give an additional $102 million to help stamp out the disease. In his annual letter describing the Foundation’s priorities for the coming year, Gates wrote, “We are so close, but we have to finish the last leg of the journey.”

This latest infusion of funding was announced in January at the annual World Economic Forum in Davos, Switzerland, days after the Gates Foundation announced a $100 million partnership with the Abu Dhabi government that will also devote about $34 million to eradicating polio in Afghanistan and Pakistan, with the remaining $66 million going toward the delivery of a vaccine for pneumococcal pneumonia.

Polio was once a global menace that struck fast and left many of its victims, such as US President Franklin Delano Roosevelt, paralyzed for life. The introduction of the Salk vaccine in 1955 and the Sabin vaccine in 1962 changed the course of the epidemic dramatically. Polio was largely eliminated in industrialized countries by the early 1980s, and an effort to vaccinate millions of people in poor countries has managed to rid the disease from all but a handful of countries. Last year, the World Health Organization (WHO), which oversees the Global Polio Eradication Initiative, reported fewer than 1,000 new polio cases, most of them in four endemic countries: Afghanistan, Pakistan, India, and Nigeria.

The quest to make polio the second disease in modern history to be eradicated—smallpox was the first—has been a long and expensive process. Public health authorities have already spent 22 years and $6 billion trying to eliminate the virus.

D.A. Henderson says the smallpox eradication campaign that he led for the WHO took 14 years and cost roughly $500 million in today’s dollars. In contrast, he said, polio eradication is costing about $1 billion a year. Still, David Heymann, previously the WHO representative of the director-general for polio eradication and now with the Epidemiology and Infectious Diseases Department at the London School of Hygiene and Tropical Medicine, believes it would be foolish to give up now. “It would be a shame to stop before you have finished the job,” he says.

There are many challenges to eradicating polio in endemic countries. Massive floods last year in Pakistan exacerbated the spread of polio, which is transmitted in food and water contaminated with fecal matter. Political instability and lack of security have prevented vaccination teams from reaching children in both Afghanistan and Pakistan, while a vaccine shortage, inadequate maps, and poor surveillance efforts left about 20% of Nigeria’s children unvaccinated. High population density and poor sanitation are the main reasons polio persists in the states of Uttar Pradesh and Bihar in northern India.

The trivalent oral polio vaccine, known as tOPV, which contains weakened versions of three types of wild poliovirus, also has had lower efficacy (74%) in Uttar Pradesh and Bihar than in the remainder of India (85%)—possibly because the substandard living conditions make children from this region more prone to diarrheal diseases that can prevent the vaccine from working effectively. Also, the strains in the trivalent vaccine can interfere with each other, producing immunity to one strain but not another.

Oliver Rosenbauer, a spokesperson for the Global Polio Eradication Initiative, says last year there were only 42 cases of polio reported in these two Indian states, compared to 741 cases in 2009. Rosenbauer says this dramatic decline may be partly due to the introduction of a bivalent vaccine known as bOPV. —Regina McEnery

Researchers and Advocates Consider Advantages of More Adaptive Clinical Trial Designs

At the AIDS Vaccine 2010 meeting last September, several researchers began discussing the benefits of employing so-called adaptive trial designs in the evaluation of HIV vaccine candidates (see A Change of Tune, IAVI Report, Sep.-Oct. 2010). Since then, this idea has been gaining momentum. On Feb. 10-11, 2011, the World Health Organization, the Joint United Nations Programme on HIV/AIDS, the Global HIV Vaccine Enterprise, IAVI, and the National Institute of Allergy and Infectious Diseases (NIAID) sponsored a meeting in New York City to discuss the current state of thinking on the use of adaptive clinical trial designs in HIV vaccine development. The meeting brought researchers, clinical trialists, regulators, and vaccine advocates, including several developing country representatives, together to discuss the opportunities and challenges associated with this approach.

Simply put, adaptive clinical trial designs are those that allow modifications to an ongoing trial based on interim data. These modifications can include everything from altering the number of volunteers to discontinuing an arm of the trial. All of these changes must be planned for and described in the trial protocol before it gets underway.

Such adaptive trial designs are not new—they are commonly used in other fields of research and have already been employed to some extent in HIV vaccine clinical trials. The biggest difference between the HIV vaccine trials conducted to date and some of the adaptive designs being considered now is that the proposed designs would involve multiple arms testing different vaccine candidates, each compared to a single placebo arm, and would allow for investigators to discontinue one of the vaccine arms if it was underperforming compared to the other candidate. The goals of this type of adaptive clinical trial design are to evaluate more candidates, more quickly, with fewer resources. “We don’t have a vaccine candidate that we want to trot into a Phase III trial,” said Dean Follman, a statistician from NIAID.

Nearly 30 years after the first diagnosed case of AIDS, only a handful of vaccine efficacy trials have been conducted, a pace many researchers lament is much too slow. But one of the many unanswered questions on the use of multi-candidate adaptive clinical trial designs for HIV vaccine trials is whether there are enough eligible candidates to support this approach.

Other questions that were discussed during the two-day meeting included how and when to communicate trial alterations to the volunteers, under what circumstances the adaptive design is preferable to the standard two-arm trial, how to convince multiple vaccine manufacturers to consider having their vaccine candidate tested head-to-head against another, and what regulatory authorities would expect to approve such trial designs. These questions remain largely unanswered for now, but they will likely be discussed and debated more in the coming months. “It’s all manageable but logistically difficult,” said Pat Fast, chief medical officer at IAVI. —Kristen Jill Kresge