Killing two birds with one stone: A new vaccine to fight rabies and MERS-Cov

In 2003, the world was faced with a serious biological threat. The severe acute respiratory syndrome (SARS) virus hit the scene in China and quickly spread to 28 countries across the globe. The reason for the rapid and global spread lay in the very nature of the virus' infection. It can be spread by close person-to-person contact through respiratory droplets produced when an infected person sneezes or coughs, and the initial symptoms of disease are very non-specific. This allowed the virus to easily be carried via international travel throughout the world. While the number of cases quickly rose to a total of 8,098 within 6 months, the global response was also rapid. The World Health Organization quickly activated their global alert system and began aiding countries in identifying and quarantining those infected and at risk. Thanks to this global response, SARS was quickly handled. However, this virus showed the world how at-risk we are to respiratory viruses in an age of increasing global travel.

Since the 2003 SARS outbreak, scientists have been on the look-out for the SARS virus and other related viruses in an attempt to minimize outbreaks. These viruses are part of a family known as Coronaviridae, specifically the coronavirus sub-section of this family (a typical virion is shown to the right). They are single-stranded, positive sense RNA viruses, which means that as soon as the virus invades a host cell, it can begin making its own proteins and progeny immediately without the need for time for replication or transcription of the genetic material. The coronaviruses that cause respiratory syndromes infect the cells of the lungs, leading to severe and sometimes deadly pneumonia.

In 2012, a novel coronavirus was identified in Saudi Arabia; it was named the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). It quickly spread to the United Kingdom through travel. While the MERS-CoV has never caused an outbreak as large as that of the SARS virus, it has also not been contained as successfully. MERS-CoV outbreaks have continued to pop up from 2012 to now, with the most recent outbreak update coming just last week from Saudi Arabia. The MERS-CoV outbreaks have caused a total of 1,905 confirmed cases in 27 countries, with 677 deaths. The severe pneumonia caused by MERS-coV is more deadly than that caused by SARS and other coronoviruses, leading to the alarmingly high 37% death rate.

There are currently no vaccines and no treatments for MERS-CoV. Quarantining those infected and using additional precautions when treating these patients have been the only successful preventative measures to reduce spread. The biggest problem for complete elimination of this virus is that, unlike the SARS virus, the MERS-CoV can also infect an animal that has frequent contact with humans: camels. In many parts of the globe, camels are essential for transportation and play a pivotal role in the economy. Since camels have been shown to be a reservoir for the MERS-CoV, and people in these regions need to continue to have close contact with these animals, the virus has an easy route to re-enter the human population even with the implementation of the same control measures that were so successful with the SARS virus.

The MERS-CoV can be spread from camels to humans in many ways.

Recent work has focused on elimination of virus from the camel population as a course of action to reduce human infections. Starting with a rabies vaccine, which has long been given to animals and is well-tolerated, a group in the United States has shown that immunity to both rabies and MERS-CoV can be achieved in mice. In order to do this, they took a piece of the MERS-CoV spike protein and fused it to the rabies G protein. This allowed a portion of the MERS-CoV to be incorporated into the rabies virus vaccine particles for delivery to the mice. After receiving the immunization, mice were challenged with the MERS-CoV and were found to be protected from infection. The researchers also found high levels of neutralizing antibodies against both MERS-CoV and the rabies virus in the blood of the mice.

While this vaccine candidate is still in the early stages of development, the successful use of the previously tested and approved rabies vaccine as a backbone may provide a way to shorten the timeline to implementation of the vaccine for animals on a larger scale. This could provide a way to start to eliminate the MERS-CoV reservoir and begin to reduce outbreaks in people across the globe. While other research groups are still searching for human vaccination and treatment strategies that will greatly improve our ability to decrease disease severity and save lives, dealing with this large camel reservoir will be an essential step before disease elimination and eradication can truly be considered.

The not-so-loving kissing bug

As fall approaches and the weather begins to cool from the stifling heat of summer, we all like to spend a bit more time outside enjoying the air. Unfortunately, this is the perfect time for insects who like to feed on our blood and potentially carry disease to come out and join us. Most people think of ticks and mosquitoes when they think of insects that carry disease, but there is another major player in the Americas: the Triatominae, also known as the kissing bug. This little creature can carry a parasite known as Trypanosoma cruzi, which causes Chagas disease.

The Triatominae insect, aka the kissing bug, that
can carry the Trypanosoma cruzi parasite that
causes Chagas disease.
Image from Snopes.com

Chagas disease is a major global health threat, with 70 million people at risk of exposure and approximately 5.7 million people becoming infected each year. The disease mainly affects Latin America, but thanks to population flows and increases in vector populations, the disease has been spreading to the north, with cases reported in the US in Texas, in Canada, and even in Europe. The disease exists in two phases, the acute phase and the chronic phase. During acute infection, there are large numbers of parasites in the blood, but symptoms are few and non-specific. There can be fever, headache, swollen lymph nodes, or even completely asymptomatic cases. As the disease transitions into the chronic phase, the parasites sequester into the muscle of the heart and digestive tract. This can result in severe cardiac and digestive disorders, which can last for years after the original infection began. Most dangerously, heart failure can result, causing death.

Treatment for Chagas disease remains a major issue. There are very effective treatments for the acute phase, with almost 100% efficacy, but these treatments are underutilized. Treatment requires rapid diagnosis of the disease, which is often difficult due to the non-descript or non-existent symptoms. Also, the drugs need to be administered over a very long duration, 60-90 days, leading to low follow-through rates for treatment to completion. Unfortunately, there are currently no treatments for the chronic phase.

Current work being done at the University of Georgia is working to address one of these problems. They are focused on developing affordable diagnostic tests that can be used anywhere to diagnose Chagas disease in the acute phase. Their efforts focus on increasing the number of T. cruzi antibodies being detected in the test in order to allow for a more sensitive test. Not only will the test help identify people who have the disease, but it will also improve the ability to monitor how well a person is responding to treatment, hopefully allowing for decreases in treatment times.

Beyond the work at the University of Georgia focusing on improving diagnostics, there has also been a lot of effort into developing new treatments for Chagas disease. The Drugs for Neglected Diseases Initiative has chosen Chagas as one of their focus diseases and has been working on new therapeutics to treat both the acute and chronic phases of disease. Their goal is to develop an orally administrated treatment that will require less than 30 days of administration by 2020. They have moved into a Phase II proof of concept study with two different treatment options, with results expected late this year and early next year.

While advances are being made in detection and treatment of Chagas in humans, there are also many animals that are threatened by this disease. Chagas disease can also affect both wild and domestic animals, making elimination of the parasite reservoir impossible. Notably, Chagas disease in dogs is known to be frequently fatal, causing the same heart failure and cardiac symptoms seen in humans with chronic Chagas disease. For dogs, there is currently no available treatment for the disease. 

The best way to deal with Chagas for the time being is the prevent it. Insecticide spraying is encouraged by the World Health Organization and has been shown to decrease the incidence of disease. Also, being able to identify the Triatominae insects when they are seen can help people avoid areas where they could become susceptible to being bitten. These bugs are known to enjoy living in hay, woodpiles, and under porches, so avoiding these areas can help reduce transmission of the parasite. 

To protect yourself and your furry friends this fall, be sure to be on the lookout for the kissing bug. One kiss from this little love bug may just be your worst first date ever.