Novavax Study Reveals mRNA Vaccine Trigger Surges in IgG4—Is this Troubling?

Scientists employed by U.S. headquartered vaccine manufacturer Novavax conducted research comparing IgG subclass and Fc effector function profiles following repeated vaccination with the recombinant Spike (rS) protein SARS-CoV-2 vaccine (NVX-CoV2373, Novavax, Inc.) in comparison to a single rS vaccination following repeated mRNA vaccinations. Why? Because, according to the company’s recent preprint paper, repeated vaccination with COVID-19 mRNA-based vaccines (Pfizer-BioNTech/BNT162b2 or Moderna/mRNA-1273) associates with marked surges in the proportion of immunoglobulin G4 (IgG4) in spike-specific responses and reductions in Fc-mediated ADCP and ADCD that may limit control of viral infection. In this laboratory-based study led by Raj Kalkeri, associate director Novavax and affiliated with University of Melbourne, at the Peter Doherty Institute for Infection and Immunity and Lisa Dunkle, M.D. , Vice President Global Medical Lead for Coronavirus vaccine, the team reports after repeated vaccination with mRNA-based COVID-19 vaccines, IgG3 reaches peak titers after the second dose, then steadily declining to markedly lower levels by the third and fourth doses, but IgG4 surges. Generally, in lower amounts (0-5% of total IgG), IgG4, the Novavax team observes, slowly increases over time because of “repeated or excessive exposure to some antigens.” Kalkeri and Dunkle report that greater amounts of IgG4 can become problematic, leading to not only immunosuppression as well as poor clinical outcomes concerning COVID-19 but also could trigger autoimmune disorders and anti-inflammatory IgG4-related diseases. Following repeated mRNA vaccination, IgG4 was observed to increase from 0.04% of total SARS-CoV-2 spike–specific IgG after two doses to 19.27% after three doses.

According to some researchers, excess IgG4 associated with COVID-19 mRNA vaccine may lead to immunotolerance while others, such as Dr. Mikolaj Raszek of Canada-based Merogenomics, suggest a potential connection to cancer, the later speculative at this stage.