Breakthroughs Blog: Vaccines

As 2015 draws to a close, the Global Health Technologies Coalition is reflecting on the past year in global health innovation. Below, in no particular order, are our picks for the top global health research and development (R&D) news and stories that shaped 2015. First ever vaccine against dengue virus approved The world’s first vaccine against dengue fever was approved by the national regulatory authority of Mexico, marking an important initial step in preventing this mosquito-borne infection, which is spreading worldwide. Nearly half the world’s population now lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine’s developer Sanofi spent over 20 years and US$1.65 billion developing the vaccine and is now pursuing regulatory approval in 19 other countries. Sanofi has stated it will make the vaccine available for sale at a “fair, affordable, equitable, and sustainable price.” NIH finally receives funding boost Christmas came early for the US National Institutes of Health (NIH). After years of stagnated funding, NIH—the world’s leading public funder of neglected disease R&D—will finally receive a funding boost in 2016. In the fiscal year 2016 omnibus spending package, Congress approved a $2 billion—nearly 7 percent—increase in funding for NIH from $30 billion to $32 billion. NIH has lost 22 percent of its purchasing power since 2003 due to inflation, so this boost will provide critically-needed funding for the agency to continue to build upon its record of leadership in global health R&D. Photo: PATH/Satvir Malhotra Availability of the first child-friendly, appropriately-dosed TB medicines announced Health workers will soon have a critically-needed new tool to improve treatment for the one million children infected with tuberculosis (TB) each year. In November, TB Alliance and partners announced that the first-ever appropriate, child-friendly tuberculosis (TB) medicine in the correct dose will be available in early 2016. At the moment, TB medicines are not available in appropriate doses for children, so parents must crush or cut the pills to administer. This arduous process—combined with the bitter taste—leads to poor adherence. The new treatments are strawberry- and raspberry-flavored, appropriately-dosed versions of the three most commonly used TB medicines. These new treatments are expected to significantly improve TB treatment and adherence among children. Global Health Innovation Act passes House An important new piece of global health legislation championed by GHTC—the Global Health Innovation Act—passed the US House of Representatives earlier this month. This legislation would strengthen global health R&D programming at the US Agency for International Development (USAID) by directing USAID to incorporate R&D across its global health programming and requiring the agency to report annually to Congress on its R&D programs and activities. In 2016 the hard work will begin again to get the Senate to introduce and pass companion legislation so the bill can move another step closer to becoming US law. Ebola product development advanced at lightning speed After years of slow and stunted progress in the development of drugs, vaccines, and diagnostic tools to fight Ebola, product development jumped forward by leaps and bounds in 2015. Thanks to the collaboration of developers, regulatory agencies, and the World Health Organization, six Ebola diagnostics were developed and deployed in West Africa under emergency measures, early-stage clinical trials are underway for at least two Ebola drug candidates with others in development, and at least 15 vaccine candidates are in development with two candidates undergoing Phase II/III trials. The most advanced vaccine candidate VSV-EBOV was shown to offer near-total protection, according to preliminary data analysis from the trials. While these products arrived too late to have a major impact during the epidemic, the accelerated development approaches and mechanisms used may be able to be emulated to speed product development in the future. New pediatric malaria treatment receives positive scientific opinion paving path for regulatory approval A new pediatric malaria medicine— Pyramax® Granules—will soon be available for children worldwide. In November, Pyramax® Granules received a positive scientific opinion from the European Medicines Agency (EMA) under Article 58, a mechanism which facilitates regulatory approval of the product in malaria-endemic countries. The medicine, which was developed by Medicines for Malaria Venture (MMV) in partnership with Shin Poong Pharmaceutical Co. Ltd, is a combination of two antimalarials and is designed to be easy for children to consume. It is taken in liquid form and is flavored to mask the bitter taste. Next, MMV and Shin Poong will work to introduce Pyramax® Granules as well as Pyramax®, the tablet version which is suitable for adults, in malaria-endemic countries. Several promising global health products advancing through development The pipeline of global health technologies is growing and maturing with several exciting products moving through critical development stages. For example, a new medicine for drug-resistant TB became the first new TB drug to advance into clinical trials in six years when it entered Phase I trials in February, a vaginal microbicide containing a novel antiretroviral drug to prevent HIV entered Phase I trials in November, a drug candidate with the potential to become the first ever, oral-only, single-dose treatment for sleeping sickness completed Phase I trials in September, and a microbicide vaginal ring is completing Phase II trials with results expected in early 2016. Due to increased attention and investment over the last 15 years, there are now nearly 500 neglected disease product candidates in the pipeline. Global goals recognize importance of health R&D In September, global leaders ratified a new set of global goals, called the Sustainable Development Goals (SDGs), which will guide global development efforts for the next 15 years. GHTC was excited to see these goals recognize the importance of global health R&D with inclusion of a target supporting R&D of vaccines and medicines for diseases primarily affecting developing nations. It’s been broadly recognized that we cannot reach the ambitious SDG health targets—to reduce maternal and child mortality and end the epidemics of HIV/AIDS, TB, and neglected tropical diseases— by 2030 with the health technologies we have today. Now that the goals and targets are in place, accountability is key. We must ensure the SDGs translate into greater investment and political commitment from all nations to catalyze development of the next generation of health technologies needed to transform global health.

Virginia Commonwealth University (VCU) received a grant from the Global Alliance to Prevent Prematurity and Stillbirth, a member of the GHTC, to study the human microbiome in search of biomarkers to predict preterm birth. The human microbiome is comprised of all the microorganisms (i.e., bacteria) normally found in the human body and the genetic material of those microorganisms. The team at VCU will study the microbiome of women throughout pregnancy, assessing the impact of changes in the microbiome on pregnancy outcomes. Existing research has demonstrated a correlation between an imbalance in the vaginal microbiome of pregnant women and preterm birth, specifically for African Americans. A recent study out of The Rockefeller University in New York could pave the way for a new treatment against human African trypanosomiasis (sleeping sickness), a disease caused by the Trypanosoma brucei parasite and transmitted by the tsetse fly. Once in the human bloodstream, the parasite evolves, and constantly changes the proteins on its surface so that the immune system can’t recognize it. The team at The Rockefeller University determined that by blocking bromodomains—a particular type of protein—through either genetic modification of the parasite or the use of a molecule known as I-BET151, they could trick the parasite into thinking it was still in the tsetse fly. Thus, the parasite would revert to the form it takes within the fly, making it much easier for the immune system to detect and attack it. The method was tested in sleeping sickness–infected mice, and those treated with I-BET151 survived much longer than their counterparts. Child receiving a vaccine. Photo: PATH/Robin Biellik The world’s first vaccine against dengue fever—a mosquito-borne disease that causes fever, headache, and, muscle and joint pain—has been approved for use in people aged 9 to 45 by the national regulatory authority of Mexico. Nearly half the world’s population lives in dengue-endemic countries, and an estimated 390 million infections occur each year. The vaccine, which cost US$1.65 billion to develop over 20 years, is projected to generate $1.4 billion in sales by 2020. Sanofi, the pharmaceutical company that developed “Dengvaxia,” is currently pursuing regulatory approval in 19 other countries and has stated that the vaccine will be sold at a “fair, affordable, equitable, and sustainable price.”

In this guest post Tom Harmon, senior policy analyst at the International AIDS Vaccine Initiative (IAVI), and Anna Forbes, a globally recognized advocate for women’s HIV prevention needs, discuss a new piece proposing how HIV prevention research and development (R&D) for women and girls can better align with programs to improve their health and well-being. Photo: PATH/Doune Porter Around the time a girl in sub-Saharan Africa reaches the age of fifteen her risk of HIV infection skyrockets from two to five times that of boys her age. This high incidence stands in contrast to the increasing success of the global HIV and AIDS response, which has seen global infections reduced year after year and millions more people living with HIV and AIDS able to access lifesaving antiretroviral treatment (ART). It’s not news that HIV and AIDS has increasingly impacted young women and girls in sub-Saharan Africa. Fortunately, this past year may be remembered as a year the world stepped up to the challenge. The 2015 launch of the US$500 billion dollar DREAMS program (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe women) by the US President’s Emergency Plan for AIDS Relief (PEPFAR), the Bill & Melinda Gates Foundation, and Girl Effect aims to leverage high-impact interventions to reduce new HIV infections by 40 percent in girls and women in ten countries in Africa by 2017. Even as this program was scaling up, the World Health Organization expanded HIV treatment guidelines to cover all individuals living with HIV and AIDS regardless of the extent to which the virus has impacted their immune system status. This expansion will include many women and girls not previously covered. These near-term efforts should make a substantial difference in women’s lives. It’s also encouraging that pre-exposure prophylaxis (PrEP)—just a few years after formal approval as an HIV prevention tool—is incorporated in DREAMS. We know that the optimal HIV prevention toolbox for women and girls is one that can be customized to meet each person’s individual needs. Continuing to expand that toolbox with other new HIV prevention options, including HIV-blocking microbicides and a preventive HIV vaccine, can ultimately break the back of the rising epidemic among women and girls and the global epidemic in the long-term. Research to develop and deliver effective new prevention options doesn’t take place in a vacuum—it must take into consideration the wider needs of the women and girls it seeks to ultimately protect. To that end, IAVI recently published a new policy brief “Research and Development of New Biomedical HIV Prevention Tools for Women and Girls: Combating the global AIDS epidemic through a more empowered response in sub-Saharan Africa” that summarizes findings and recommendations for improved HIV prevention research with and for women and girls. Our work highlights challenges to better align HIV prevention research for women and girls with the needs and realities of their lives. For instance, a recent issue of the Journal of Acquired Immune Deficiency Syndromes highlighted the relatively low participation of women in HIV vaccine trials (38 percent) and AIDS treatment trials (19 percent), which limits our understanding of how effective an intervention is for women and girls. And, we know that if research taking place in a community doesn’t ensure some ongoing community benefit once a trial is completed, it can discourage participation by women in future trials. Fortunately, some of these essential elements are already being addressed. Positive results in microbicides research have correlated to excellent efforts to incorporate end user perspectives in product profiles. The Ragon Institute’s FRESH study links girls and young women highly vulnerable to HIV with programs that build job skills, attacking one of the drivers of poverty while also identifying early HIV infection and quickly enrolling women living with HIV and AIDS in ART programs. Keeping HIV prevention R&D in touch with the renewed focus on fighting HIV and AIDS among women and girls in sub-Saharan Africa is critical to the long-term goal of ending AIDS. We’re proud to be part of an HIV prevention research community that is already making strides to improve the lives of women and girls while building the scientific knowledge necessary to bring new tools to the fight. Doing right BY communities will ensure that the fruits of our work will be more effective IN those communities. Pockets of high incidence are devastating in any population and put overall progress at risk. Infectious diseases spread in the wider world when they are not stopped where they hit the hardest. This further underscores the importance of a sustained commitment to improving and expanding programs that reduce HIV incidence in women and girls and adding new interventions that women and girls can use to protect themselves. None of this is possible if we can’t assure women and girls with a strong HIV response that engages them, listens to them, and then implements the programs and research necessary to make this feminized epidemic yesterday’s news.

Snakebites, which Médecins Sans Frontières describes as “one of the world's most neglected public health emergencies,” kill 200,000 people each year. This makes snakes the second deadliest animal after mosquitoes. However, not only has research and development for snakebite antivenoms received little investment, but production of existing treatments is also declining due to their low profitability for pharmaceutical companies. Antivenoms are traditionally developed using antibodies produced by animals that have been bitten by snakes, but a number of small biotech companies and even individuals are testing innovative ways to create new, multipurpose antivenoms. Dr. Claire Komives, a professor of Chemical Engineering at San Jose State University, is working to enlist the E. coli bacteria to produce a promising antivenom, as the use of bacteria could make production significantly cheaper and easier to scale up. Meanwhile, a team of researchers across Europe and Central America are developing a treatment for a myriad of common venoms, starting with an antivenom that is effective against three different venoms. Their plan is to identify deadly venoms against which their product is not effective and then develop and incorporate a treatment for that venom into their product. Finally, a team at the California Academy of Sciences is screening chemical compounds in existing, approved drugs to develop a product that could stabilize a bitten patient, giving them more time to seek treatment. The World Health Organization estimates that one-third of the world’s population has latent tuberculosis (TB), only 10 percent of whom will actually contract the disease. However, co-infection with a helminth, a parasitic worm, increases one’s chance of developing TB and exacerbates the symptoms, particularly lung damage. Scientists have long suspected that the parasitic infection impeded the immune system’s ability to fight TB, inhibiting immune cells that provide protection against TB. However, new research out of Washington University in St. Louis suggests that a specific molecule produced by helminths’ eggs prompts an inflammatory immune response that increases one’s susceptibility to TB and its symptoms. The team was able to engineer immune cells that do not produce the molecule, and mice co-infected with TB and the parasite who were given the engineered immune cells did not have the damaging, inflammatory immune response. Analyses of blood samples from TB patients also demonstrated a correlation between the presence of the molecule and the severity of TB symptoms. Photo: PATH/Wendy Stone Researchers at The Scripps Research Institute (TSRI) are developing an HIV and AIDS vaccine candidate that targets a region found on 90 percent of known strains of the HIV virus. The team at TSRI has been conducting experiments to prompt the immune system to generate broadly neutralizing antibodies—proteins which fight multiple strains of the HIV virus—and discovered that four of these antibodies all targeted the same part of the virus, the V2 apex. Further, two of the antibodies have an unusual advantage. While most antibodies mutate from their original form to become more effective at fighting a virus, two of the antibodies were able to bind to the V2 apex in their initial form, consequently speeding up the immune response. However, the body doesn’t naturally make a large number of these antibodies, instead focusing on the further developed antibodies. To address this, the team at TSRI engineered a version of an HIV protein to which those basic antibodies bind with the anticipation that it will lead to their increased production. The engineered protein is being used in a vaccine candidate that will next be tested in animal studies.