Breakthroughs Blog: Vaccines

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. CRISPR-cas9, a revolutionary gene editing tool, has been hailed a breakthrough device for microbiologists and geneticists—but not without certain reservations. In a study recently published in Nature, researchers attempting to target and edit genetic blindness in mice analyzed nucleotides—the single-unit building blocks for DNA—in the edited and control mice in order to evaluate success of the tool. CRISPR successfully targeted the alleles—or mutated nucleotides—causing blindness in the mice, but the editing also caused 1,600 off-target, unpredicted mutations, including 100 “large changes” in the DNA structure. This is important because single-nucleotide mutations are associated with many diseases, such as sickle-cell anemia, Huntington's disease, cystic fibrosis, and more. The researchers stressed that more needs to be done to study off-target mutations before CRISPR can be considered risk-free, but that the outlook for the tool is still positive, as any scientific tool has side effects. The science behind creating an effective vaccine that is capable of completely eradicating a disease is complex and hard-won. The only vaccine that has been used to successfully eradicate a disease in humans is the smallpox vaccine. Edward Jenner used cowpox, a similar but much less dangerous bovine variation of the disease, to create a successful vaccine against smallpox—and now scientists are going back to that methodology in an attempt to eradicate malaria. Scientists plan to genetically modify a rodent-variation of the malaria parasite to then use on healthy human volunteers. The hope is that the variation will result in a protective response in humans. The first phase of trials will begin in 2018 and will involve studying initial protection against the disease, with future phases focusing on continued efficacy of the vaccine. Motivated by a lack of awareness and funding for tuberculosis (TB), Médecins Sans Frontières, or Doctors Without Borders, launched a clinical trial, entitled  TB PRACTECAL, aimed at finding a new, improved treatment for drug-resistant TB. The trial, which officially launched in January 2017, is testing an innovative combination of TB drugs that will only need to be taken for six months. Current treatments for drug-resistant TB are physically and emotionally arduous, painful, and only successful about 50 percent of the time, which is why shorted, improved treatment regimens are needed. The first set of trial results is expected to be released within two years with final results within four. If successful, the organization hopes the new treatment will be rolled out in countries around the world and mark an important step forward in combatting the global epidemic.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. A recent Congressional hearing on Zika has revealed that there is a lack of consensus regarding the diagnosis and treatment of the virus. Furthermore, only approximately 25 percent of babies born from women who have been exposed to Zika receive the necessary follow-up to evaluate their children for developmental defects. Such follow-up is critical—Zika can cause defects in the infant months after birth. As a result, the impact of Zika may be underestimated, leaving public health professionals uneasy about proposed budget cuts by the Trump Administration, which could exacerbate the treatment and reporting challenges that characterize the current outbreak. Chagas disease, colloquially known as "kissing bug disease," is more deadly than previously thought due to underreporting of the disease. Going undiagnosed while carrying Chagas can elevate the risk of death, primarily due to associated heart problems that will develop over time. Chagas disease initially mimics symptoms of the flu, often causing a misdiagnosis and lack of proper treatment, and it can lie symptomatically dormant for years, silently causing irreparable damage to the heart. There is currently no effective vaccine against the disease. The Democratic Republic of Congo’s (DRC) Ministry of Health has approved the use of an experimental Ebola vaccine to combat the outbreak. The vaccine, though experimental, proved to be highly effective in clinical trials. Details of how the vaccine will be deployed have not been announced yet, but if further cases are confirmed, it will likely be given to contacts and contacts of contacts of those with a confirmed case. So far, there have only been two confirmed cases, but over fifty suspected cases.

Researchers at the University of Cape Town discovered a compound that blocks the cycle of malaria within the human body, regardless of its drug-resistant status. The compound acts a preventative tool as well as a treatment for those infected with malaria, as it can block transmission and prevent infection. The compound, MMV390048, began phase I clinical trials in 2014, but subsequent data has not yet been published. The drug will enter phase II clinical trials this year in Ethiopia, and it is hoped this drug will be on the market within the next ten. With the world circling in on polio eradication, global public health professionals have run into a major obstacle that makes ridding the disease incredibly complicated: A vaccine shortage. There currently isn’t enough injectable polio vaccine for the world to use, as demand is so high. There isn’t enough of the vaccine in production for each child to receive two shots, which is what researchers suggest to protect against contracting polio. An alternative is the oral polio vaccine, but due to its heightened risk of complications, professionals believe this vaccine will soon be phased out. While polio vaccine manufacturing may be ramped up to treat children in the next few years, it is essential that health care professionals continue to vaccinate children ten years post-eradication to ensure there is no resurgence of the disease. Funders, including the Gates Foundation, are now putting efforts toward the next surge in vaccine demand, and hope to overcome this obstacle to reach global eradication of polio once and for all. An outbreak of Ebola has been confirmed in the Democratic Republic of the Congo (DRC), and health researchers around the globe are working to distribute an experimental vaccine. While the outbreak is contained due to the geographic isolation of the cases, the WHO and Gavi are still working quickly toward an effective and globally approved vaccine that can be used in future outbreaks. The DRC has not requested a vaccine at this point in time, but these organizations are prepping for when the country requests it, or for if the outbreak spreads past the DRC. The vaccine is experimental, and requires special modes of transportation, yet proved incredibly successful during the Ebola outbreak of 2014.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. For many years, ineffective treatment plans and archaic diagnostic tools have stood as a barrier to tackling tuberculosis (TB). More recently, new drugs and diagnostics have emerged. Yet, availability has not always translated to widespread access. For example, despite the availability of new rapid diagnostic tools like GeneXpert, it is estimated that over 40 percent of new TB cases go undiagnosed or are not reported and use of older, less accurate sputum tests still outpace use of the GeneXpert. Though new drugs like bedaquiline and delamanid are not available, more than 75 of patients who need them do not have adequate access. A number of hurdles to adoption and scale-up exist from lack of funding for TB programs to high costs to implementation failures Action is needed by global leaders and innovators to break down these barriers if the global community wants to achieve its goal of eradicating TB by 2030. Malaria is more complex than scientists previously thought. In a recent study published in the Proceedings of the National Academy of Sciences, scientists used DNA fingerprinting to track malaria on a cellular level. They found that the parasite has a heightened level of genetic recombination developed during meiosis, leading to a wide variety of malaria strains. This suggests that malaria can evade immune system response, acting as a chronic disease—and it means there is no one-cure-fits-all solution. Because of the incredible amount of genetic diversity malaria can have in the body, one vaccine solution may not work for all individuals, casting doubt on the efficay of vaccines now in development. While this discovery makes malaria harder to prevent and eradicate, scientists have also discovered that malaria isn’t as transmissible as it first seemed, with the parasite only causing five or six secondary cases from one original infection, whereas it was previously thought one case could subsequently infect dozens of individuals. The International Partnership for Microbicides (IPM) has announced a clinical trial that is hopeful to significantly reduce cases of HIV in Sub-Saharan Africa and around the world. The clinical trial will use the IPM-developed dapivirine ring, a small silicone ring inserted in the vagina, releasing a contraceptive (levonorgestrel) and an anti-HIV drug (dapivirine). The ring is easy to insert and lasts three months. Building on the previous ring that only released dapivirine, having the ring also act as a contraceptive will not only reduce the likelihood of HIV infecting women, but will also provide women with the choice to protect against unwanted pregnancy. This trial is especially important because women are most at-risk for contracting HIV, especially in countries with low rates of condom use. IPM hopes to have the ring ready for shipment globally by 2020.