New data suggest it may be vaccine or bust.

In what seems like 10 years ago, but was actually just 6 weeks ago, on this very website, I said this:

“This is COVID that allows us to open up more quickly, assuming antibodies are protective, which, let’s be honest, if they aren’t we’re sort of screwed no matter what.”

Cut to a couple of days ago, when I come across this article in Nature – the first deep dive attempting to answer the question of just how protective those coronavirus antibodies are.

And, at first blush at least, the news isn’t great.

Researchers recruited patients who had recovered from COVID-19 from the Rockefeller University Hospital in New York. The 111 individuals enrolled had to have been asymptomatic for at least 14 days. They also recruited 46 asymptomatic household contacts and some controls who had never had COVID-19.

Now, a brief refresher on antibodies. There’s several different types, but we broadly think about immunoglobulin M as the acute antibody, generated in the throes of the illness and immunoglobulin G as the long-term antibody. But here’s the thing – the mere presence of antibodies does not mean those antibodies are protective. The researchers tease this apart for us.

They zeroed in on two types of anti-coronavirus antibodies, a group that binds to the spike protein – that’s the crown part of the corona, and more specifically, antibodies that bind to the receptor binding domain of the spike protein – this is the key, if you will that opens the door of your cells (a receptor called ACE2) to infection. It’s a good bet that if there is an antibody that will shut down the virus, it’s one that will block the receptor binding domain.

Should we start with the good news?

Compared to controls, IgG and IgM levels were higher among those who had recovered from COVID-19. As expected in this convalescent group, a bigger difference was seen in IgG compared to IgM. You can see in this graph that IgM levels seem to go down a bit over time.

And, I’ll note, about 20 – 30% of people didn’t have antibody titers significantly above controls. But, broadly, ok – the majority of people made antibodies.

But that’s not the key thing here. Were these neutralizing antibodies? Do they stop viral replication?

To figure this out, the researchers genetically engineered a SARS-COV-2 pseudovirus which expressed the spike protein and let it run amok infecting ACE2-expressing cells in culture.

They then added varying dilutions of patient plasma to the petri dishes to determine how much plasma you’d need to shut the virus down by 50%, the so called “neutralizing titer” 50 or NT50.

The results here were not so encouraging.

33% of the individuals tested had an NT50 of less than 50, which implies essentially no immunity to repeat infection. 79% had an NT50 less than 1000 – they may have partial immunity. Only two people tested had an NT50 greater than 5000.

Higher overall antibody titers were associated with neutralizing ability, as might be expected.

And individuals who had been hospitalized for COVID-19 were more likely to have neutralizing antibodies than those who hadn’t been hospitalized, suggesting those with more severe illness are more likely to be immune in the future.

Overall, this is fairly concerning. Without neutralizing antibodies, an end to coronavirus transmission seems unlikely. But let’s also remember the empiric data – we don’t yet have any significant numbers of individuals who have been documented to have cleared COVID-19 and then become re-infected. And even without high levels of neutralizing antibodies, a second infection is likely not to be as bad as the first.

And there’s another nugget of hope in this study. The researchers didn’t stop by simply measuring how many people had neutralizing antibodies. They actually sequenced 89 different anti-covid antibodies to determine which specific antibodies were highly neutralizing.  They identified 52 that had neutralzing ability and several that had potent neutralizing ability – targeted to specific amino-acids on the receptor binding domain.

And here’s the thing – most of the people in the study HAD those highly neutralizing antibodies – they just weren’t the main antibodies they were producing. Why is this good news? Because it suggests a pathway for a successful vaccine – we can make these potent neutralizing antibodies – it’s just that many of us don’t. But a vaccine designed to promote that particular antibody response could be highly successful.

All in all – this was a study that suggested the tunnel we are in now may be a bit longer than we had hoped, but it also shows a light at the end.

This commentary first appeared on medscape.com