Breakthroughs Blog: Research Roundup

An experimental, aerosol vaccine completely prevented infection from Ebola in monkeys, and will be tested in human clinical trials shortly. The vaccine was tested on twelve monkeys, with four each receiving one and two doses, two receiving a liquefied version of the vaccine, and a control group comprised of the remaining two monkeys. Four weeks after vaccination, all 12 monkeys received a massive dose of the virus, 1,000 times the fatal amount. While the two unvaccinated monkeys became ill, all ten of the vaccinated monkeys remained healthy, and the researchers found no trace of the virus in their blood. Aerosol vaccines are easy to administer and do not require a trained health professional, and thus are ideal for use in an outbreak or a country without a robust health workforce. Earlier this year, Apple Inc. launched ResearchKit, an open source software framework to facilitate the collection of health information in clinical trials, and soon two major pharmaceutical companies—GlaxoSmithKline and Purdue Pharma—may be utilizing the software. The software makes it easy for researchers to create their own iPhone applications to connect with participants in clinical trials and is already being used by academic institutions and nonprofits for data collection. Not only can these applications survey participants, but they can measure hand tremors in patients with Parkinson’s disease, physical activity in relation to cardiovascular disease, and geographic locations that exacerbate the symptoms of asthma. The software provides researchers more frequent access to a greater number of participants. Researchers are also looking into connecting other devices to the software, for example, asthma inhalers that transmit data via Bluetooth. While smartphones, and in particular iPhones, are less prevalent in low- and middle-income countries, the software could be used by health professionals or researchers for data collection. Already, smartphones are being used to perform eye exams in Kenya, pasteurize milk for breast milk banks in South Africa, and could soon be used to detect infection with Loa loa filariasis in Africa. Photo: CDC/ Dr. Mae Melvin Researchers at the Duke-NUS Graduate Medical School in Singapore have discovered an antibody—a protein in the immune system that identifies and combats specific pathogens—against one of the four viruses that causes dengue fever. The team, led by Shee-Mei Lok, a professor of Emerging Infectious Diseases at the university, first identified the specific part of the virus that triggers the production of antibodies in mice and believes that a vaccine comprised of just that part of the virus could provide protection from infection. Lok hopes to create a cocktail treatment against dengue fever using antibodies against each of the four types, and the team is continuing their research to identify an antibody against DENV-4, the one virus responsible for dengue fever for which there is not a known antibody. Bats are the natural reservoir, or host, for more than 65 viruses, bacteria, and other pathogens that infect humans, including Ebola, rabies, and the coronaviruses responsible for SARS and MERS. A team of researchers surveyed 1,270 people in rural Ghana, shedding light on the interactions between bats and humans and consequently, how these diseases are transmitted to humans. Two-thirds of respondents reported physical contact with bats, with 37 percent having been bitten, scratched, or exposed to the urine of bats. While only 17 percent of Ghanaians reported interacting with bats at work or at home, nearly half regularly visit bat caves.

Photo: CDC/ Melissa Dankel With the looming threat of a post-antibiotic era—in which minor infections are fatal due to growing drug resistance—world leaders are examining remedies for treating bacterial infections from the pre-antibiotic era. One such treatment, known as phage therapy, uses live viruses that attack bacteria and ignore human cells. The method, which was discovered in the early twentieth century, was largely abandoned after the discovery of penicillin and is currently only in use in Russia, Georgia, and Poland. Nearly a century later, the European Commission is funding a US$4.2 million clinical trial to test phage therapy on 220 patients in France, Belgium, and Switzerland. The study will use a cocktail of these viruses—known as bacteriophages—developed by French company Pherecydes Pharma. Phage therapy is expected to be an option of last resort to treat infections that are resistant to three or four drugs. American pharmaceutical company Johnson & Johnson will initiate clinical trials of an experimental HIV vaccine that completely prevented HIV infection in half of the monkeys that received the shot. Vaccinated and unvaccinated monkeys were exposed to simian immunodeficiency virus—a relative of HIV—on six occasions, after which all of the unvaccinated monkeys were infected. The clinical trial will include 400 healthy volunteers from the United States, East Africa, South Africa, and Thailand. If the vaccine appears to be safe and effective, Johnson & Johnson plans to commence phase 2b trials within the next two years. Each year, a new flu vaccine is developed to protect against the three to four strains of the influenza virus that are expected to be most virulent. The vaccine is comprised of antibodies—proteins developed by the immune system—against those selected strains. However, new research out of Rockefeller University could pave the way for the development of a universal flu vaccine that would provide lifetime protection against all strains of human influenza. The team at Rockefeller noticed that humans naturally develop sialylated antibodies—antibodies with sialic acid at one end—after receiving a seasonal flu vaccine, specifically the H1N1 vaccine. The team then vaccinated mice with either the standard H1N1 vaccine or an experimental vaccine that included sialyated antibodies against H1N1. The two vaccines provided equal protection from H1N1, however, only the vaccine containing sialyated antibodies provided protection against other strains of H1 influenza. In the lab, the researchers determined that the sialic acid allows antibodies to attach to human immune cells as well as the virus, and consequently coordinate the human immune response by prompting the production of broadly protective antibodies, rather than antibodies specific to one strain of the virus. The US Court of Appeals for the Second Circuit—one of 12 regional courts in the United States that reviews decisions made by local, district courts—upheld a district court’s decision against “product hopping,” a mechanism by which brand name pharmaceutical companies prevent competition from generic manufacturers by slightly adapting a product and removing the original from the market. In this case, pharmaceutical company Actavis had altered Nameda, a drug for Alzheimer's disease, and planned to remove the original version from the market, claiming that the new version is superior. However, the court ruled in People of the State of New York v. Actavis PLC that such action would be “unlawfully anticompetitive” and would violate the US Sherman Anti-Trust Act. The exclusivity period of the original version of Nameda was set to expire in July 2015, after which time generic versions of the drug could enter the market, while the exclusivity period of the new version would not expire until 2029. The court’s decision states that Actavis’ motivation for removing the original version from the market was to inhibit sales of generic versions of the original formulation of Nameda, as automatic substitution laws allow pharmacists to provide a generic version when a brand name drug is prescribed.

Testing for tuberculosis in the lab. Photo: PATH/Mike Wang A new study published in PLOS Medicine indicates that multi-drug resistant tuberculosis (TB) is less contagious than drug-susceptible TB. Researchers followed 1,055 “household contacts”—relatives, neighbors, or friends living in close proximity—of 213 patients with multi-drug resistant TB and 2,362 household contacts of 487 patients with drug-susceptible TB for three years in Lima, Peru. Contacts of patients with drug-susceptible TB were nearly 50 percent more likely to become infected, with 4.8 percent developing the disease compared to 3.3 percent for contacts of multi-drug resistant TB patients. According to Dr. Louis Grandjean, the study's lead author, the TB bacteria experiences a "'fitness' cost" in which it becomes less infectious as it mutates to become resistant to antibiotics. The authors note, however, the possibility that future strains of drug-resistant TB could develop to be fitter. The Indian Ministry of Health is proposing major reforms at the Central Drugs Standard Control Organization (CDSCO)—the national regulatory authority of India. The proposal seeks to improve the CDSCO, using the US Food and Drug Administration (FDA) as its model. One of the key reforms would be a major increase in staffing, from 561 employees to 1,800 by 2025, and the Ministry of Health estimates that the overhaul would cost US$272 million. The announcement comes as the FDA ramps up inspections of foreign pharmaceutical manufacturing plants, and after several high-profile crackdowns on Indian manufacturers. The government of the Republic of Equatorial Guinea has committed $36.75 million for phase 2 and 3 clinical trials of an experimental malaria vaccine, in partnership with three oil and gas companies—Marathon Oil Corporation, Noble Energy Inc., and AMPCO—which will be contributing an additional $11.75 million. The vaccine was developed by Sanaria Inc. and initial trials suggest that it is both safe and effective. The funding will cover additional trials with 450 participants in 2016, and 3,000 participants in 2017 to 2018. The government of Equatorial Guinea and Sanaria Inc. have also signed an agreement to explore the possibility of establishing clinical laboratories and vaccine manufacturing centers in Equatorial Guinea. GHTC member Treatment Action Group and Yale University’s Global Health Justice Partnership filed a federal lawsuit against the FDA for withholding clinical trial data for two costly hepatitis C drugs that were approved by the FDA in December 2013 and October 2014. Both drugs were developed by pharmaceutical company Gilead Sciences and are intended to cure, not merely treat hepatitis C, according to the complaint, which also notes that 12-week regimens of the drugs cost $94,500 and $84,000, respectively. The two advocacy organizations requested the release of the clinical trial data from both Gilead Sciences and the FDA; Gilead denied the request, and the FDA responded that it will take 18 to 24 months to even consider releasing the data. Treatment Action Group and the Global Health Justice Partnership are arguing that the FDA’s response violates the US Freedom of Information Act, and that the data is needed so that doctors, patients, and policymakers can evaluate the “safety, efficacy, and cost-effectiveness” of the drugs.

A woman's hands holding a SILCS diaphragm. (Photo: PATH/Patrick McKern) Last week, GHTC member PATH launched the Caya® contoured diaphragm in the United States, after developing and testing nearly 200 prototypes to ensure the product was safe, effective, and user friendly. PATH collected input from women and health care providers across the globe throughout the research and development (R&D) process, ultimately creating an innovative contraceptive that protects against sexually transmitted infections, has no side effects, and is discreet, comfortable, easy to use, and “one-size fits-most." The Caya® diaphragm, which is now available in 25 countries, is an important addition to existing contraceptive options, as it is the first diaphragm introduced in the United States in 50 years. In 2014, the World Health Organization (WHO) recognized the Chinese Food and Drug Administration as a functioning regulator; China has now developed two vaccines—for Japanese encephalitis and influenza—that have received WHO prequalification, a sign that a product is safe and effective. A representative of the Bill & Melinda Gates Foundation, which has worked with the Chinese government to enhance its vaccine R&D capacity, said that the second prequalification “may be the start of China truly becoming a player in global health.” China recently established a system that regulates manufacturing for pharmaceutical products based on the European Medicines Agency’s (EMA) and US Food and Drug Administration’s (FDA) standards. However, China’s regulatory system still has some barriers to overcome, as the regulatory approval process takes much longer than the EMA’s or FDA’s. Additionally, the Chinese government requires vaccines and drugs to be packaged individually—which is not conducive to international shipping—and there are currently no guidelines on how a manufacturer can obtain a license in China if clinical trials are conducted abroad. A vaccine candidate for the Middle East Respiratory Syndrome (MERS) has been successfully tested in mice and will progress to Phase I clinical trials shortly. The vaccine uses a weakened strand of a poxvirus—known as Modified Vaccinia virus Ankara—that has been altered to display a certain protein unique to the MERS virus. The immune system recognizes the protein as foreign, and develops antibodies and T cells to combat MERS. In the lab, the MERS virus was not able to reproduce in vaccinated mice despite exposure to “high levels” of the virus. The vaccine was developed by the Ludwig Maximilian University of Munich’s Institute for Infectious Diseases and Zoonoses, and the German Center for Infection Research has already committed 1.5 million euros for the Phase I clinical trials. The results of a massive trial for a new pneumonia vaccine were announced last week, demonstrating a major reduction in cases of the disease responsible for fifteen percent of deaths in children under five years of age. The vaccine, known as PCV-10, protects against ten different bacteria that can cause pneumonia. The trial lasted seven years, during which time the vaccine was given to 35,000 children in the Kenyan town of Kilifi. Eighty percent of vaccinated children demonstrated greater resistance to pneumonia. The town saw a 42.7 percent reduction in cases overall, and a 95 to 100 percent reduction in invasive pneumococcal disease—the most deadly form of pneumonia.