Doc, do Coronaviruses have any dirty tricks like having their infectious properties enhanced by antibodies? Are subunit vaccines more successful because they elicit only a single antibody clone, perhaps not evoking the particular paratope a virus would utilize to defeat the immune system?
My coronavirus immunology is not strong but from what I've gleaned from listening to the TWiV and Immune podcasts is that they don't currently mimic other viruses that can enhance disease through antibodies. The classic example of antibody-dependent enhancement (ADE) of disease is found in dengue virus infections. Dengue viruses have four distinct serotypes. Serotypes are defined as viruses that do not induce a neutralizing immunity to other viruses of the same family. Typically when an individual is infected with one serotype of dengue virus they won't show signs of severe disease. If that same individual is infected with a second serotype they have an increased chance of hemorrhagic fever. The mechanism that has been proposed behind ADE is that antibodies produced during recovery in response to the first serotype cross-react with the second serotype once it enters the body. Unfortunately, the cross-reactive antibodies can't neutralize the second serotype but some bind to the virus particles, which are then taken up by cells more easily, increasing the vial load of infection and the bodies response to fight off the virus. This is thought to lead to the hemorrhagic fever.
ADE does not seem to be a contributing factor to COVID. So far SARS-CoV-2 is only a single serotype and due to it's low mutation rate is very likely to remain so, making neutralizing antibodies effective against the virus rather tha enhancing virus uptake. The other piece of evidence that doesn't support ADE for SARS-CoV-2 is that convalescent sera is effective at treating COVID patients. Whether antibodies to other coronaviruses could cause ADE is still an open question as far as I know but if I recall they're further removed from each other antigenically than the serotypes of dengue viruses.
Having said that, an article in PNAS,
Avoiding pitfalls in the pursuit of a COVID-19 vaccine, discusses ADE and also cell mediated enhancement of disease in vaccine development. The vaccine development is going to require carefully controlled trials to ensure safety.
Subunit vaccines are typically not the best approach for viral infections. As far as I know there are only three available; these prevent hepatitis B, HPV infection and shingles. HBV and HPV are very basic vaccines that just seem to work. The shingles vaccine is to a glycoprotein, gE, of varicella-zoster virus (VZV). It's not clear how this vaccine works but gE is very import for the replication cycle of VZV. It is produced on the cell surface during infection and it's likely that both and antibody-mediated and T-cell-mediated immune responses are induced that makes the vaccine effective. The skew in the type of antibody and T-cell response might be key, which is very likely down to the adjuvate used. As I mentioned before, the adjuvant is very aggressive and it does cause significant inflammation at the injection site, which is a good indicator of an immune response. A small price to pay given the vaccine's efficacy and the potential severity of shingles.
I'm of the opinion that SARS-CoV-2 does not need an advanced vaccine approach for the immediate future. It just needs to work well enough to get the R value below 1.
