I think almost all the evidence points in the opposite direction, unless I’m drastically misunderstanding something, which does occasionally happen.
First and foremost, the idea of having a binary seroconversion dependent on germinal center response seems highly contraindicated at best. There are a billion studies showing that single doses of vaccines give some antibody response, and then a second dose gives far more (often 2-3 OOM). For example, 1, 2, 3, 4, etc. This is the point Lanrian seemed to be making, which I think pretty immediately disproves the hypothesis.
This isn’t just COVID either—many vaccines have this pattern of giving boosters to increase antibody count. And not only does it increase count, secondary responses vastly increase antibody affinity and produce different antibody types, e.g. the primary response is more IgM whereas secondary response produces more IgG and IgA (the latter aiding especially in mucosal immunity). [Citations for this can be found on pgs 413-414 of the Janeway immunobiology book, and I can maybe link pictures.]
On this note: higher doses of vaccine straightforwardly give higher antibody levels from a nonzero baseline, inconsistent with a binary response [1].
Further, amount of NAb present in the infected scales with disease severity—it isn’t a binary, which you’d expect to see if the main correlate of immunity was a single threshold of GC response. [1 shows correlation with severity, 2 “great titer variability, 3 amazing paper showing different neutralization levels translates well to efficacy in vaccines, plus waning titer and loss of efficacy over time.]
A different important departure from a binary condition: a substantial number of cases exhibit rapid waning of NAb levels over 6 months to a negligible concentration (and cases fall all over the spectrum for how fast they wane) [this great Lancet study]. Presumably this could be easily overcome with another vaccination, as asked.
Another datapoint against is that it doesn’t explain partial vaccine efficacy. How would a vaccine protect you from mortality but not from symptoms, unless it mattered where on a spectrum you landed? (Obviously there are ways, but they all strain credulity.) It also wouldn’t fit with the fact that vaccines can result in NAb titers that are universally high in a group, but still leave them getting occasionally infected [I’ve lost this source but it was obviously relevant for Delta strain, though many people produced no or little NAb for Delta which was an important distinction].
Last, even if we were totally dependent on a binary GC response, we could probably still modulate that with more introduction of antigen! My understanding of GC responses is that they get initialized in part through other cells like CD4+ T cells, the concentration of which also correlates with different doses of vaccine, presumably causally.
I just read this tonight and it is fantastic. You know more immunology than me by a lot! <3
I’ll be editing my answer to leave the substance of what I wrote so posterity can see me being dumb but willing to make an educated guess, but defer to your answer at the top with an explanation :-)
I think almost all the evidence points in the opposite direction, unless I’m drastically misunderstanding something, which does occasionally happen.
First and foremost, the idea of having a binary seroconversion dependent on germinal center response seems highly contraindicated at best. There are a billion studies showing that single doses of vaccines give some antibody response, and then a second dose gives far more (often 2-3 OOM). For example, 1, 2, 3, 4, etc. This is the point Lanrian seemed to be making, which I think pretty immediately disproves the hypothesis.
This isn’t just COVID either—many vaccines have this pattern of giving boosters to increase antibody count. And not only does it increase count, secondary responses vastly increase antibody affinity and produce different antibody types, e.g. the primary response is more IgM whereas secondary response produces more IgG and IgA (the latter aiding especially in mucosal immunity). [Citations for this can be found on pgs 413-414 of the Janeway immunobiology book, and I can maybe link pictures.]
On this note: higher doses of vaccine straightforwardly give higher antibody levels from a nonzero baseline, inconsistent with a binary response [1].
Further, amount of NAb present in the infected scales with disease severity—it isn’t a binary, which you’d expect to see if the main correlate of immunity was a single threshold of GC response. [1 shows correlation with severity, 2 “great titer variability, 3 amazing paper showing different neutralization levels translates well to efficacy in vaccines, plus waning titer and loss of efficacy over time.]
A different important departure from a binary condition: a substantial number of cases exhibit rapid waning of NAb levels over 6 months to a negligible concentration (and cases fall all over the spectrum for how fast they wane) [this great Lancet study]. Presumably this could be easily overcome with another vaccination, as asked.
Another datapoint against is that it doesn’t explain partial vaccine efficacy. How would a vaccine protect you from mortality but not from symptoms, unless it mattered where on a spectrum you landed? (Obviously there are ways, but they all strain credulity.) It also wouldn’t fit with the fact that vaccines can result in NAb titers that are universally high in a group, but still leave them getting occasionally infected [I’ve lost this source but it was obviously relevant for Delta strain, though many people produced no or little NAb for Delta which was an important distinction].
Last, even if we were totally dependent on a binary GC response, we could probably still modulate that with more introduction of antigen! My understanding of GC responses is that they get initialized in part through other cells like CD4+ T cells, the concentration of which also correlates with different doses of vaccine, presumably causally.
I just read this tonight and it is fantastic. You know more immunology than me by a lot! <3
I’ll be editing my answer to leave the substance of what I wrote so posterity can see me being dumb but willing to make an educated guess, but defer to your answer at the top with an explanation :-)
The relevant graphics on booster shots: