Seth Berkley

Scientific and policy challenges to development of an AIDS vaccine

24 years since the identification of HIV as the causal agent of AIDS the pandemic continues to outpace attempts at control. The response to HIV/AIDS has been inadequate and has consisted of crisis management rather than purposeful public health policies because of the early silent spread of the virus its high incidence in high-risk populations its uniformly fatal outcome if not treated and its global proliferation. However an unprecedented commitment to control HIV has begun. In 2005 G8 leaders agreed to provide prevention and treatment to all those in need by 2010. But however well intended a universal treatment paradigm is unsustainable. UNAIDS predicts that more than US

Thorny issues in the ethics of AIDS vaccine trials.

9 billion will be needed in the next 2 years to fund AIDS treatment and care in the developing world alone. Estimates suggest that for each person who starts antiretroviral treatment at least six people are newly infected with HIV. Thus even if existing programmes are rapidly expanded with increases in financing infrastructure and human capacity the AIDS pandemic will continue to outpace efforts to curtail it unless we can substantially improve prevention strategies and their implementation. (excerpt)

HIV vaccine trials in India

At this week’s US National Institutes of Health AIDS vaccine meeting and the upcoming 13th International Conference on HIV/AIDS and Sexually Transmitted Infections in Africa the need for vaccine trials in high-incidence developing countries and associated ethical concerns is high on the agenda. (excerpt)

Ending an Epidemic: The International AIDS Vaccine Initiative Pioneers a Public-Private Partnership

To the editor: As CEO and president of the International AIDS Vaccine Initiative (IAVI; New York), I am writing to protest against a news brief “HIV vaccine controversy” in your March issue1, which I regard as both tendentious and inaccurate. First, it is impossible for a phase 1 vaccine trial—like the one of the AIDS vaccine candidate tgAAC09 that IAVI co-sponsored in Belgium, Germany and India—to establish that a candidate “had failed to protect trial participants.” A phase 1 trial generates safety and initial immunogenicity data on a vaccine candidate; it does not test efficacy. The volunteers in a phase 1 AIDS vaccine trial are low-risk individuals unlikely to ever be exposed to HIV, so it is not possible to asses protection against HIV infection. At issue was one trial with two arms: one in Europe, one in India. Because vaccinations began first in Europe, some preliminary data became available from Europe soon after vaccinations began in India. Those data suggested tgAAC09 was safe and well tolerated. As part of a safety trial, researchers also measure volunteers’ immune responses to a vaccine candidate to help determine the appropriate dose and schedule for further testing. The preliminary data from Europe showed tgAAC09 elicited only modest immune responses, but this was no reason to discontinue the Indian arm of the trial, as your news brief suggests. Typically, when vaccinations are halted in a phase 1 trial, it is because of evidence that a candidate is not safe or is poorly tolerated by volunteers; there was no such evidence in this case. The trial protocol was designed to include 80 volunteers, 30 of them in India, and without data from the cohort in India the phase 1 trial results would have been incomplete. India was included in the multi-country design of the trial in part because the vaccine candidate was matched to the subtype of HIV prevalent in India, clade C; in Europe, clade B HIV is prevalent. TgAAC09 was considered promising because it performed well in preclinical studies; had the candidate eventually proven effective in human trials, having data from India and other places in the world where clade C HIV is common would be important. Thus, it was valuable to test the candidate in a part of the world where the vaccine, if effective, might eventually have done the most good, to lay the groundwork for possible future licensure. Also, the trial was designed as an international study in part to determine how the vaccine candidate would behave in different populations. The safety and immunogenicity data from Indian and European volunteers might have differed owing to environmental or genetic factors that can affect immune responses. According to your account, the Indian Council of Medical Research (New Delhi), which, like IAVI, co-sponsored the phase 1 tgAAC09 trial in India, “stopped the trial in December, saying the vaccine gave ‘poor’ immune responses.” In fact, the trial was not stopped; it was completed as planned in January 2007. When data from all arms of the phase 1 trial of tgAAC09 were collected and analyzed, researchers were able to confirm that the vaccine candidate was safe and well tolerated in all populations tested. The candidate produced an immune response in 17% of trial volunteers at the highest dose tested. This information served precisely the purpose for which immunogenicity data in a phase 1 trial are intended: it indicated that a higher dose might be necessary. In a subsequent phase 2 trial of tgAAC09 conducted in three countries in Africa, a higher dose of the vaccine candidate was used, and this also proved safe and well tolerated. Unfortunately, even at the highest practical dose, the candidate, in IAVI’s view, did not generate sufficiently robust immune responses to justify further testing as a stand-alone vector. The reality of vaccine development is that the vast majority of experimental vaccines and other pharmaceutical candidates do not advance past phase 1 and 2 trials. But from every properly conducted trial, whatever its result, comes new knowledge that helps to illuminate the search for more effective candidates. Your report finally claims that IAVI is “stuck in an ethical quagmire” because participants in the trial now “test seropositive for HIV” and cannot convince their employers that this is because they were immunized as part of an AIDS vaccine trial. This is completely erroneous; given the nature of the vaccine candidate, not a single volunteer in the tgAAC09 trial in India tested positive for antibodies against HIV. Such a scenario has occurred in other trials of vaccines against AIDS and other diseases. When it happens in AIDS vaccine trials, volunteers are offered a certificate that explains to an employer or any other interested party that their HIV antibodies are due to participation in an AIDS vaccine trial and not to actual HIV infection. IAVI’s conduct throughout testing of tgAAC09 was consistent with its model to work with in-country partners to ensure the highest ethical and operational standards, and we remain committed to developing a safe, effective AIDS vaccine for use throughout the world, especially in those regions in greatest need.

Ending cervical cancer: A call to action

than 25 million people and more than 40 million are infected today with HIV, the virus that causes AIDS. The spread has been worldwide but it is the developing world that is now bearing the brunt of the epidemic with 95% of the new infections. Despite increasing efforts at prevention and treatment, the epidemic, continues to accelerate. This year, according to UNAIDS, has seen the largest number of deaths to date, more than 3 million, with more than 5 million new infections. With 14,000 new infections a day, HIV is already reversing decades of progress in these developing countries and has the potential to be even more catastrophic. Only a vaccine has any hope of ending the AIDS epidemic, yet through the mid-1990s AIDS vaccine work was limited on the world’s richer nations, and even this work had slowed to a standstill. In 1996 I founded the International AIDS Vaccine Initiative (IAVI), a public-private partnership to advance the development of HIV vaccines for use globally, and particularly in the areas most affected by HIV and AIDS. IAVI faced great skepticism that a non profit could advance vaccine research and development. Yet only four years later, in August 2000, British physician and parliamentarian Evan Harris became the first person to be vaccinated with an HIV vaccine designed for Africa, using strains of the virus circulating in that region. In 2001, trials of this product began in Kenya, the first time an AIDS vaccine was tested in that country. The vaccine turned out to be ineffective—but IAVI’s model of working with academia, governments, and companies to speed product development and ensure an international focus was clearly effective. Today IAVI, a fully integrated vaccine development effort managed by experienced industrial project managers, is the second largest global program in HIV vaccine research and development, with more than forty active R&D relationships. IAVI has successfully translated innovative technologies into seven novel vaccine candidates that have entered human trials in the last six years, and has conducted clinical studies at 15 trial sites located in 11 countries. The Seth Berkley

The Need for a Vaccine

The outlook for elimination of the scourge of cervical cancer is bright, because we now have the tools to achieve this goal. In recent years human papillomavirus (HPV) vaccination in high‐income countries has resulted in dramatic decreases in HPV infection and associated cervical disease. If all countries with a substantial burden of disease introduce the vaccine nationally, we can protect the vast majority of women and girls most at risk. For women who are beyond the vaccination target age, progress has been made in screening and treatment for cervical precancer, but we must accelerate this momentum to reduce incidence and mortality worldwide to the very low rates found in wealthier countries. Human and financial resources must be increased and directed to programs that follow best practices and reach all women, including the marginalized or disadvantaged. Seven key actions are recommended. Now is the time for action at national, regional, and global levels.

Health security's blind spot

There is no question that there is a critical global need for an HIV vaccine that can protect all people from the varying HIV viruses circulating around the world. This effort has been woefully underfunded and underprioritized. HIV vaccine development is now beginning to get more of the attention it deserves and resources are slowly following. It is clear that the world should be investing far more in the search for a vaccine and prioritizing the creation of vaccines that will be appropriate for use where the epidemic is spreading most rapidly. Furthermore, it is clear that a system must be put in place to assure that all those who need a vaccine will have access to one, regardless of their economic or social status. The latter relies heavily on international efforts to aggressively move R&D forward and to begin to prepare for success.

Syria, slums, and health security

The severity of this years influenza virus is a reminder of the daunting task facing the global health community as it struggles to prevent infectious diseases from sparking deadly epidemics. Today, yellow fever and cholera continue to spread in Africa, while Brazil is in the midst of a major yellow fever outbreak. It was only recently that Zika virus and Ebola virus epidemics were in the headlines. The world needs to harness every resource and tool in the battle to catch outbreaks before they catch us. Prevention is always the first line of defense, and nations must maintain vigilant surveillance—and yet, effective and affordable, quick and definitive diagnostics are absent in the countries where they are most needed. This represents one of our most serious global health security blind spots.

The need for a global HIV vaccine enterprise

The Syrian conflict has been described as a new kind of world war: local conflicts with resounding global consequences. It has accelerated the rise of the terrorist group ISIS, destabilized Europes open border agreement, and led to the single largest refugee crisis in decades. These factors contribute to an emerging fragility that compounds the humanitarian crisis in Syria but also threatens global health.