Wednesday, February 15, 2017

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.