This article largely addresses the challenges of vaccine development for SARS-CoV-2.
It was extremely clarifying for me. It seems to have consulted several experts for opinions, but is written for close-to-layman reading.
Here are a few bullet-points, but I recommend the whole thing.
- Th-2 type immunopathology, "in which a faulty T cell response triggers allergic inflammation," plays a big role in bad vaccine response to SARS-CoV-2
- Ralph Baric: "There is the potential for ADE, but the bigger problem is probably Th2 immunopathology"
- Me: Th-2 responses are extensively documented in both severe COVID19 disease, and SARS-1's bad vaccine responses. This makes a lot of sense. I would like to understand what is upstream of that, sometime.
- Another likely problem: Complement system malfunction
- "poorly functional antibodies that form immune complexes, activating the complement system and potentially damaging the airways"
- Me: There is most likely a scientific term for this phenomenon. I'll add it when I find it.
- ADE is possible, but less than likely to play a major role
- FIPV is a coronavirus where ADE is a major concern. But FIPV productively infects macrophages. I've seen no evidence so far that SARS-CoV-2 productively infects WBCs.
- UPDATE: It looks like it isn't productively replicating in WBCs, but it probably is fusing with them and telling them to apoptose. Receptor uncertain, but they were checking T-cells specifically, which are exactly the WBCs that get severely depleted in severe COVID-19. Consider me pretty convinced. Article, h/t CellBioGuy. (P.S. SARS-2 is much better at this than SARS-1.)
For RSV* (Respiratory Syncytial Virus) and SARS-1, bad vaccine response gets blamed on both Th-2 immunopathology and antibody complexes activating the complement system. This can lead to severe disease, including the infiltration of lung tissue by neutrophils (for both) and eosinophils (for RSV?).
For SARS-1, whole-S-protein vaccines seemed more likely to produce this detrimental enhanced immune response. S-fragments containing only the receptor binding domain offered protection, but did not produce this unwanted effect.
They are hoping that the same logic and fix goes for SARS-2, but are still waiting on the test results.
*Me: Side-tangent, but both SARS and RSV seem to be nasty lung infections with some propensity to form syncytia in severe disease. Heck, one of SARS-2's novel mutations seems likely to be involved in increased syncytia formation. However, the viruses are not close relatives, and they seem to show different preferences for which particular lung cells they reshape into syncytia. I find it interesting that they ran into a similar bad reaction here.