Friday, 6 September 2013

More MERS molecular masterfulness: Egyptian camels contain lots of anti-MERS-CoV antibodies [AMENDED]

UPDATE #1: 23NOV2015
Perera and colleagues from China, Japan, Egypt and the United States report in Eurosurveillance that they
have found a high prevalence of Egyptian camels which have antibodies to a piece of the Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein.

The group looked at 1,343 human sera (815 from Cairo as part of influenza study; 528 archived from Hong Kong) and 625 animal sera (from goats, sheep, water buffalo, cows, camels, pigs and birds) from Egypt and China (no MERS reported there, so this acts as control population; unfortunately no camels tested from there either). 

A positive control serum was provided by Prof Drosten from an earlier MERS case.

The novel assay does not need to be used in a biosafety level 3 containment environment (BSL2 is fine) because it does not use whole/live MERS-CoV to capture the human/animal antibodies, rather it uses just a piece of the virus; the spike protein, which is known to attract the lion's share of antibody attention. 

The spike protein was merged with HIV (non-infectious) proteins to create a pseudoparticle of proteins that could enter cells, and also bind to MERS-CoV antibody which would act to prevent such entry by the virus-like particle. If there was no antibody, the pseudoparticles could enter cells and this entry could be measured using a marker enzyme reaction. This novel assay (pseudoparticle neutralization test; ppNT) was run in parallel with a more standard micro-neutralization (MNT) test; the two tests agreed well but the standard MNT test needed to be carried out in a BSL3 laboratory).

The more traditional MNT test pre-incubated infectious MERS-CoV with serum and then measured whether the live MERS-CoV could still infect and damage cells. If there was antibody in the serum, it blocked infection (as it presumably can in us during a second or third infection). 

Pseudoparticle/virus will be more or less blocked from cell entry if more or less antibody is present in the serum. One can determine how much antibody was in the serum sample too. These type of tests measure the ability of antibody in a patient/animal to block virus entry; it's neutralizing ability. 

A high proportion (103/110; 93.6%) of dromedary camels from Egypt had antibodies that could block cell culture infection by a lab strain of the MERS-CoV (MERS-CoV/EMC from Erasmus University Medical Center). 

No humans had antibodies. No animal sera from China (Hong Kong) were positive - this included pigs (n=260) and wild birds (n=204). 

Numbers were sometimes very low but no goats (n=13), sheep (n=5), water buffalo (n=8) or cows (n=25) were antibody-positive in Egypt. Only the camels.

The authors specify that this does not exclude cross-reactivity with a closely related, but non-MERS, CoV that has at some previous point infected the camels. If only there was some sort of plan to do this sort of virus hunting in mammals.
Click to enlarge.

So how does this fit in with the human acquisition model proposed 1-week ago? Pretty well. It supports previous findings from Omani camels too. 

Camels could be part of the chain of infection. It says nothing about how they may then go on to be a source of human infections that start off as a respiratory illness, presumably requiring, at least in most cases anyway, inhalation or self-inoculation (I'm looking at you, nose-pickers). For that we'd need to know anything about survival of MERS-CoV in excreta and on surfaces. I'd also like to see some more animal test results. 

Nonetheless, it looks as though we have some very useful antibody detection assays shaping up, and they can do just that.

Here's hoping for a KSA study next.

UPDATE #1: Fixed some typos and grammar.