Tuesday, June 27, 2017

MERS-CoV In Camels: The Gift That Keeps On Giving


















#12,580


This summer will mark the 5 year anniversary of the discovery of the MERS Coronavirus, and we are just shy of 4 years since camels were pegged as the likely zoonotic conduit of the virus to humans (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus).
After nearly 6 months of denial that their beloved camel could carry such a deadly disease, Saudi officials announced in the spring 2014 that work would begin on a vaccine (see Health announces the imminent arrival of a global company specialized to discuss manufacturing a vaccine against Corona).

But, as I wrote in April of 2014's Obstacles To A MERS Vaccine, after more than a decade of trying, we still had no safe and effective SARS vaccine, and the development of a MERS vaccine was likely several years away – assuming one could be created at all.

After discussing the SARS vaccine failures, I wrote:
A vaccine for non-humans – most notably camels – could possibly be created and tested quicker than a human vaccine, but early research suggests that camels are susceptible to re-infection despite having high antibody titers (see EID Journal: MERS Coronavirus In A Saudi Dromedary Herd) which raises questions over how well a vaccine would work in dromedaries
I wasn't alone in questioning a timely MERS vaccine, of course. The fast-track to a vaccine narrative was coming mainly from the Saudi government, who were battling a major nosocomial outbreak in Jeddah at the time (400+ cases), and desperately needed something positive to report. 
Since then, we've seen additional evidence that humans may not develop long-lasting antibodies to MERS either. 
In In April of 2016, in EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, we looked at a study that tested 9 Health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), that found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.

This waning antibody response in all but the most severely affected patients raised a number of interesting, and potentially serious, questions.
  1. Are those who only experienced mild or moderate illness at risk of re-infection?
  2. Would convalescent plasma donated by those without severe illness be less or ineffective?
  3. Does this skew (under count) the community seroprevalence studies we've seen coming out of Saudi Arabia and Kenya?
  4. How will all of this play into the development of a MERS-CoV vaccine (for camels or humans)?
We revisited this topic again last May, in EID Journal: MERS-CoV Antibody Response After 1 Year, where researchers followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.
Today we've a new study published in Emerging Microbes & Infections with an impressive pedigree (Webby, Poon, Peiris, et al) that tracks two camel herds between September 2014 and May 2015, and pretty much removes any doubts that camels can be reinfected by the MERS virus, despite having substantial antibody titers.

A finding that significantly complicates vaccine creation. I've posted some excerpts from the open access study below, follow the link to read it in its entirety:

Longitudinal study of Middle East Respiratory Syndrome coronavirus infection in dromedary camel herds in Saudi Arabia, 2014–2015

Open

Maged Gomaa Hemida1,2,*, Abdulmohsen Alnaeem3,*, Daniel KW Chu4,*, Ranawaka APM Perera4,*, Samuel MS Chan4, Faisal Almathen5, Emily Yau4, Brian CY Ng4, Richard J Webby6, Leo LM Poon4 and Malik Peiris4

ABSTRACT


Two herds of dromedary camels were longitudinally sampled with nasal and rectal swabs and serum, between September 2014 and May 2015, and the samples were tested for Middle East Respiratory Syndrome (MERS) coronavirus RNA and antibodies. Evidence of MERS-CoV infection was confirmed in one herd on the basis of detection of virus RNA in nasal swabs from three camels and significant increases in the antibody titers from three others. The three viruses were genetically identical, thus indicating introduction of a single virus into this herd.
There was evidence of reinfection of camels that were previously seropositive, thus suggesting that prior infection does not provide complete immunity from reinfection, a finding that is relevant to camel vaccination strategies as a means to prevent zoonotic transmission.

INTRODUCTION

Middle East Respiratory Syndrome coronavirus (MERS-CoV) was initially identified in Saudi Arabia in 2012.1 As of 5 December 2016, there were over 1800 laboratory-confirmed cases.2 Camels are known to be the natural host for MERS-CoV and the source of zoonotic infection.3, 4, 5 Zoonotic transmission events may be mild and unrecognized but may lead to transmission between humans, thus leading to MERS outbreaks in health care facilities.6, 7 The SARS epidemic of 2003 was heralded by repeated small zoonotic outbreaks in 2002 that were self-limited until a strain of SARS CoV that was well adapted to humans emerged and led to a global epidemic that affected approximately 8000 patients in 25 countries across five continents.8 Given this demonstration of the capacity for novel coronaviruses to emerge from animals to cause major outbreaks in humans, the threat from MERS-CoV remains a cause for global health concern.

Vaccination of dromedary camels has been proposed as a means to reduce the threat of zoonotic MERS.9 It is therefore important to establish the epidemiology of MERS-CoV transmission within camels, and especially whether prior infection protects against subsequent reinfection. We therefore carried out a longitudinal study of two camel herds in the Kingdom of Saudi Arabia to elucidate MERS-CoV infection and transmission.


(SNIP)


The present study provides conclusive evidence that reinfection of previously seropositive camels can occur. This observation has important implications for the feasibility of using vaccination of camels as a means to control MERS-CoV transmission within camel herds with the aim of reducing zoonotic transmission.
Reinfection in previously seropositive animals may occur because MERS-CoV infection in camels is a mucosal infection and the serum antibody might not be an accurate predictor of the effective mucosal antiviral immunities that can provide sterilizing immunity. None of the studies to date, including our own, have tested for evidence of mucosal IgA immunity in the oral or nasopharyngeal cavity, and this deficiency remains a crucial gap in the understanding of protection from reinfection.

The lack of protection against natural reinfection in the field thus raises questions about the potential duration of protection conferred by MERS-CoV infection or vaccines.
         (Continue . . . . )


None of this means that researchers won't eventually develop a MERS vaccine for camels, only that there are substantial challenges to doing so.
What we won't know - with any certainty - is how long any vaccine candidate  would be protective until long-term follow up studies are completed on vaccinated animals. 
A process that will add significant time to the development/testing cycle of any vaccine trial.


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