Tuesday, June 14, 2016

Study: Lung Immunopathology In Vaccinated Mice After Challenge With MERS-CoV


A little over three years ago, when the number of known MERS cases in the world was still in double digits, there were a lot of `forward looking' statements put forth by governments and drug companies (and ballyhooed by the media) about research into creating a MERS-CoV vaccine.

While the thought of having a MERS vaccine available in a year or two was undoubtedly reassuring to the public, it wasn't terribly realistic.

The reality was researchers had already spent 10 years trying (and failing) to produce a safe and effective vaccine for another deadly coronavirus; SARS.

Given the similarities of the two viruses, in May of 2013 I wrote a blog called  Challenges To Developing A Coronavirus Vaccine which outlined the long and frustrating search for a SARS vaccine (which remains ongoing)

This included a 2012 PLoS One research article that found that mice vaccinated with four different experimental SARS candidate vaccines developed the expected antibodies, but they also experienced lung damage when challenged with the virus.

Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus

Chien-Te Tseng, Elena Sbrana, Naoko Iwata-Yoshikawa, Patrick C. Newman, Tania Garron, Robert L. Atmar, Clarence J. Peters, Robert B. Couch
These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.

This was a topic we would revisit several times, including again in 2014's Obstacles To A MERS Vaccine.  

While MERS hasn't (yet) managed to spread widely, there are other coronavirus threats out there (see PNAS: SARS-like WIV1-CoV Poised For Human Emergence), so perfecting a coronavirus vaccine for our arsenal could someday be a very big deal. 

With the research caveat in mind that `mice lie, and monkeys exaggerate', this past week the journal  Human Vaccines & Immunotherapeutics published an eerily similar report to the one cited above, this time regarding an experimental MERS vaccine.

Short Report

To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. 
Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. 
Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.

There are several MERS vaccines under development, and this abstract doesn't tell us which one was used. And as stated previously, results obtained from lab mice don't necessarily translate to humans.

Still, this is familiar ground, and so we'll have to see where this leads.

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