TheEffectofPriorTreatment on TypeandNeutralizationof AntibodiesProducedbyMemory BCells

Notably, the composition of the memory B cells was heavily altered in the antibody group. While the absolute number of IgG antibodies rose in the antibody group compared to the control, the relative percentage fell from a vast majority to just 45%. After the second dose, IgM antibodies catapulted from marginal levels in the control to 49% in the antibody group. The researchers attribute this to the pre-exposure to anti-RBD antibodies. IgM antibodies carry far fewer mutations than IgG, meaning the antibody treatment designed to neutralize the wild-type virus was potentially predisposed to favor IgM memory B cell expression.

Upon taking a closer look at the isolated antibodies from the antibody treatment group versus the control, some major concerns are revealed. To reiterate, IgM antibodies are much more heavily concentrated in the test group than in the control group.

First, examining the binding capacity of isolated antibodies, 62% of isolated antibodies bound the wild-type receptor binding domain poorly, if at all, compared to just 5% in the control group.

The results are worse when it comes to neutralization, as only 1 of the 45 IgG antibodies and none of the 32 IgM antibodies from the test group were neutralizing, as compared to 63% of the control IgG antibodies and 17% of the IgM antibodies.

These results are attributed to shifting the target epitope in the antibody group isolated memory B cell antibodies. Whereas half of the antibodies in the control group target epitope classes one, two, or three, just 20% do so in the treatment group, favoring the class four epitope.

Discussion

This study shows that preexisting treatment with anti-SARS-CoV-2 monoclonal antibodies significantly impacts the development of memory B cell responses in post-vaccinated patients. While the initial antibody levels were not harshly impacted, in some cases even increasing, memory B cell development suffered. Affinity thresholds for memory B cell development were lowered, leading to weaker antibodies that bound and neutralized relatively poorly compared to the control.

The increase in IgM memory also aligns with previous observations of rising IgM levels post-third and fourth doses of the mRNA vaccine. The shifting memory was accelerated in the patients that previously received monoclonal treatment. However, the increasing breadth of the memory antibody responses is countered by lacking neutralization and affinity.

This is not to say stay away from monoclonal antibody treatments. They can be life-saving in many instances and should be pursued early in infection, especially for those at high risk of severe disease progression. However, once you receive antibodies, your memory responses will be altered moving forward, and you may be at risk. Continue receiving mRNA boosters every three to six months to maximize immediate protection and lasting memory against SARSCoV-2.

These studies are the first of what we hope will be many in examining the complex interaction between infection and both prophylactic and therapeutic interventions for Covid-19. The results show significant effects, particularly on memory B cells and the antibodies they produce. The consequence of these perturbations regarding protection from new variants remains to be seen, as new variants will inevitably arise. Nonetheless, we hope that these are the first of many studies investigating what is now a critical question three years into the pandemic.

Thisarticleis featuredon Forbes.org,andcan be readonlinehere: Prophylactic Antibodies Alter VaccineResponses To Covid-19