I hate to be the reviewer 2 who jumps in here to rain on the Moderna parade, but their mRNA #SARSCoV2 #COVID19 #coronavirus vaccine doesn't totally "start to look like sterilizing immunity" at day 2 post-challenge. The results are encouraging but shouldn't be inaccurately hyped. https://twitter.com/megtirrell/status/1288450703988490240

Real quick: 24 age- and sex-matched rhesus macaques got 2 doses either 10 ug or 100 ug of Moderna's mRNA-1273 vaccine 4 weeks apart and then were challenged with ~750000 PFU (plaque-forming units, or infectious virus) by combined intranasal and intratracheal inoculation.

Here's the paper in @NEJM by @KizzyPhD and colleagues. It's very well-done and shows that the vaccine is protective. https://www.nejm.org/doi/full/10.1056/NEJMoa2024671

They looked at antibody and T cell responses and whether the animals were protected from infection and COVID-19 disease pathology. Good news: some were protected from infection and all were protected from disease!

Caveat: rhesus macaques are susceptible to infection and develop pathological and clinical signs of pneumonia, but they do not develop severe COVID-19. Currently, there is no ideal, immunocompetent animal model of severe or lethal COVID-19.

The animals were protected which bodes really well for this vaccine in phase 3 trials. The results are promising but...I'm not sure I'd call this "sterilizing immunity." Check out figure 3:

Some animals from both dosing groups had subgenomic RNA in bronchoalveolar lavage fluid (a procedure in which you flush out the lungs with saline) and nasal swabs out to day 4. Subgenomic RNA indicates replicating virus and is distinguishable from residual input virus.

It's worth noting that fewer animals in the vaccinated groups had detectable subgenomic RNA compared to the control group, so some animals DID appear to have sterilizing immunity, but not all.

If there's virus replication occurring in some animals, that means there isn't sterilizing immunity, which refers to immunity that completely protects against infection. That said, this is not a "bad" or unexpected result! In fact, it's very promising.

It's not uncommon for intramuscular vaccines to provide incomplete sterilizing immunity on mucosal surfaces (like the nose). The important take-home message here is that the vaccine was protective in this animal model.

I just wish that the folks at Moderna didn't overstate the findings. Sterilizing immunity is not the standard by which all vaccines are judged & we don't need to achieve that here. Protection against disease & reduced susceptibility will provide massive public health benefits.

Bottom line: the vaccine is protective in monkeys. If this translates to humans (especially those in high risk groups), it will be a huge leap towards ending this pandemic. I was very glad to see these results. Fingers crossed for success in phase 3 clinical trials.

Also let me clarify one thing: I'm not criticizing @megtirrell's reporting here. It's important to report accurately what companies are saying about their vaccines/therapeutics in development. Just gently suggesting that companies themselves avoid overhyping results.

As I said before, these results are very good! They don't need extra spin with regard to sterilizing immunity. If this vaccine works in people the way it worked in the macaques, it will be a major breakthrough.