Breakthroughs Blog: Zika

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC

Researchers at the US National Institutes of Health (NIH) have developed a test that can rapidly screen chemical compounds for their ability to treat drug-resistant infections. The team at NIH has already put the test to use, evaluating approved medicines, promising compounds, and drug combinations against common drug-resistant bacteria. After screening an estimated 4,000 drugs and compounds, the researchers identified 25 that effectively killed drug-resistant Klebsiella pneumoniae in the lab, including not only antibiotics, but also antifungals, antivirals, antiseptics, and even anticancer medicines. The test has also revealed three drug cocktails—each comprised of three different medicines—that can effectively treat ten common multidrug-resistant bacteria. These findings will enable clinicians to prescribe drug combinations with near certainty that they will treat a drug-resistant infection without waiting on lab results. While the tool is not yet commercialized, it can be mobilized to rapidly respond to emerging drug-resistant infections. A new study has revealed that during the 2014–2015 Ebola outbreak in West Africa, the virus evolved, enhancing its ability to infect humans. Previously, Ebola was thought by many scientists to be relatively static; however, researchers at the University of Massachusetts Medical School and University of Nottingham have independently identified a mutation in the Ebola genome—A82V—that appeared during the outbreak and could have made the virus two to four times more virulent. The mutation affects the cells on the surface of the virus that are responsible for infiltrating a host’s cells. For viral cells, shape matters, as it enables them to latch onto host cells like a key in a lock. The researchers suspect that A82V adjusts the shape of these surface proteins, allowing them to better fit into human cells. The mutation also enhances the virus’ ability to infect the cells of chimps and monkeys, while hampering its ability to infect bats, dogs, cats, rats, and mice. The team also discovered that patients with the new, mutated strain of Ebola were 27 percent more likely to die. Further research is needed to confirm this finding. Last week, the NIH and the Walter Reed Army Institute of Research (WRAIR) initiated clinical trials of an experimental Zika vaccine—the first of five phase 1 trials evaluating the vaccine. The vaccine platform was first used by WRAIR in developing a vaccine against Japanese encephalitis, a fellow flavivirus. The Zika Purified Inactivated Virus (ZPIV) contains complete, inactivated virus particles that will not cause disease but train the immune system to recognize and mount a robust response to the Zika virus. In preclinical trials, the vaccine candidate successfully induced an immune response and protected animals against the virus. The five phase 1 clinical trials will test the vaccine compared to placebos in different doses and schedules, as well as in different populations, including individuals previously exposed to flaviviruses (including Zika, yellow fever, dengue, Japanese encephalitis, and West Nile) and dengue, individuals who have received yellow fever or Japanese encephalitis vaccines, and those who have received the NIH’s experimental DNA-based Zika vaccine.

The North Dakota–based SAB Biotherapeutics, Inc. has devised a way to elicit the production of human, disease-fighting antibodies in cows. Antibodies, which are produced by the immune system in response to an infection, recognize and eliminate specific pathogens. Antibodies have long been used in medicine: in the recent Ebola outbreak, antibodies from survivors were used to treat new patients. While humans can only produce 4 liters of antibodies per month—enough to treat three patients—cows produce 30 to 60 liters per month. Researchers have tried to use several mammals to produce antibodies for use in humans, but the immune system sees animal antibodies as foreign, resulting in an allergic reaction. Now, the team at SAB Biotherapeutics has designed a strategy in which cows’ antibody-producing genes are replaced with human genes. Consequently, when a cow is infected with a pathogen, it produces human antibodies in response. The company is currently testing the technology, evaluating its ability to produce antibodies against Middle East Respiratory Syndrome (MERS). While it may not be available for three to five years, the World Health Organization has already recognized the platform as one of the six most promising approaches for pandemic preparedness. The Zika virus has made headlines for its devastating impact on fetal development, and the global response has consequently focused on women who are or may become pregnant. However, new research suggests that the virus may not be so mild in men. In humans, the virus can remain in semen for up to six months, and a recent study in mice reveals that the continued presence of the virus can damage cells that are critical to reproduction. The research team at Washington University in St. Louis, Missouri, infected male mice with Zika, and within three weeks, their testes shrunk to one-tenth their original size; the seminiferous tubules—critical to producing new sperm—were damaged; and the Sertoli cells—involved in sperm growth—were dwindling in number. Ultimately, infected mice had lower sperm counts and sex hormones and were only able to impregnate a fraction of the female mice compared to their healthy counterparts. Further research is needed to determine whether Zika has the same impact on the reproductive system and fertility of human males. New drugs have made hepatitis C curable, but researchers continue to hunt for a preventative vaccine since treatment is prohibitively expensive for many patients and the virus often causes irreparable liver damage by the time of diagnosis. One protein on the surface of the virus—E2—has been a target for many vaccine candidates, however, despite its ability to induce an immune response, the protein has not successfully protected against the virus in either animal or human trials. By precisely mapping and analyzing the structure of E2, scientists at The Scripps Research Institute have discovered that E2 is an unusually flexible protein. As E2 morphs, the immune system produces an assortment of antibodies to match its dynamic shape, many of which are ineffective against the virus. Now, the team is engineering a synthetic, stable version of E2 that will generate a batch of similar, highly-effective antibodies to protect against infection.

A key target of the HIV virus is immune cells known as T cells. The virus infects T cells and hijacks the cell’s genetic machinery, enabling it to multiply and spread throughout the body. However, some T cells have genetic mutations that protect against HIV infection, and scientists at University of California, San Francisco (UCSF), are using CRISPR—a novel approach to gene editing—to insert these protective genetic mutations into ordinary T cells. First, the team used CRISPR to rapidly identify all T cell genes involved in HIV infection. Next, they inserted 149 different genetic mutations into T cells, 6 of which successfully blocked the virus. Eventually, the researchers hope that one or more of these mutations could be developed into a drug to prevent or treat HIV and AIDS. Biotech company Sangamo Biosciences is currently testing one such gene mutation that in early results appears to lower the viral load of participants. However, other studies suggest that the virus may be able to outsmart this approach, mutating until it is able to infect T cells. Consequently, an effective treatment may need to elicit multiple gene mutations in T cells, either concurrently or sequentially. Over the past five years, the Eliminate Dengue Program has released mosquitoes infected with the innocuous Wolbachia bacteria into small communities in Colombia, Brazil, Vietnam, Indonesia, and Australia. The bacteria colonizes a multitude of insect species, and while it doesn’t harm the Aedes aegypti mosquito—which spreads Zika, dengue, and yellow fever—it does prevent these viruses from replicating and blocks further transmission. Wolbachia is passed down from generation to generation of A. aegypti with each generation only living for a few weeks. Consequently, within weeks of releasing Wolbachia-infected mosquitoes into the wild, disease transmission drops drastically. Now, Eliminate Dengue will be conducting two large-scale trials in Bello, Colombia, and Rio de Janeiro, Brazil, to determine if this approach can successfully combat mosquito-borne illnesses in urban areas home to millions. The trials are funded by the United States and United Kingdom governments and philanthropic organizations the Wellcome Trust and the Bill & Melinda Gates Foundation. The highly drug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) bacteria is only susceptible to a few, last-resort antibiotics, including daptomycin, which is effective against two-thirds of MRSA infections. Now, scientists at Imperial College London have discovered how the remaining one-third of MRSA infections evade antibiotics. The bacterial cells use chemical signals to communicate with one another, however, some cells can shut down this communication system. Once that system is deactivated, the bacterial cells are able to produce decoys—molecules that have a similar outer layer to the bacteria, and consequently are targeted by the antibiotics. Thus, the antibiotics are wasted on the decoy cells and the bacterial cells are able to thrive. These findings could pave the way for new ways to treat MRSA, by combining daptomycin with a drug that interferes with the decoy system. Currently, clinical trials are underway to test such an approach, combining daptomycin with approved and experimental antibiotics that impede either the production or release of decoy molecules.