The occurrence of anti-idiotype (Ab2) antibodies and idiotype-based immunoregulation may be involved in both the antiviral treatment efficacy in SARS-CoV-2 infection and adverse effects from SARS-CoV-2 vaccines, according to an article published in The New England Journal of Medicine.
According to the anti-idiotype immune responses framework hypothesis, when an antibody is induced in response to an infection (termed an Ab1 antibody) the recombination of its variable-region antibody binding domains can create specific antibodies against Ab1 antibodies as a down regulation mechanism. A similar scenario has been proposed for T cells but with more capabilities. The researchers note that “the paratopes, or antigen-binding domains, of some of the resulting anti-idiotype (or “Ab2”) antibodies that are specific for Ab1 can structurally resemble that of the original antigens themselves.” In addition, these Ab2 antibodies may even bind to the same receptor the antigen was originally targeting and cause profound effects.
For SARS-CoV-2 infection, the researchers hypothesized that anti-idiotype responses may affect the angiotensin-converting enzyme 2 (ACE2) receptor function. The researchers noted that ACE2 performs a crucial function in regulating angiotensin responses and its engagement can influence many physiologic effects.
According to the researchers, the delineation of potential anti-idiotype responses faces several challenges due to the polyclonal nature of responses, dynamic kinetics, the simultaneous presence of Ab1 and Ab2 antibodies, and the variable expression of ACE2 across tissue and cell types. The variability in vaccine constructs will also likely have differential effects on Ab2 production.
The researchers noted that “it would therefore be prudent to fully characterize all antibody and T-cell responses to [SARS-CoV-2 and its] vaccines, including Ab2 responses over time.” They concluded that, “…much more basic science research is needed to determine the potential role idiotype-based immunoregulation of both humoral and cell-mediated responses may play both in antiviral efficacy and in unwanted side effects of both SARS-CoV-2 infection and the vaccines that protect us from it.”
Murphy WJ, Longo DL. A possible role for anti-idiotype antibodies in SARS-CoV-2 infection and vaccination. N Engl J Med. Published online November 24, 2021. doi: 10.1056/NEJMcibr2113694.