RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (IQR) 6.7–18.1%) compared to the overall memory B-cell repertoire (median 1.3%; IQR 0.9–2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
Covid should now be treated as an endemic virus similar to flu, and ministers should end mass-vaccination after the booster campaign, the former chairman of the UK’s vaccine taskforce has said.
With health chiefs and senior Tories also lobbying for a post-pandemic plan for a straining NHS, Dr Clive Dix called for a major rethink of the UK’s Covid strategy, in effect reversing the approach of the last two years and returning to a “new normality”.
“We need to analyse whether we use the current booster campaign to ensure the vulnerable are protected, if this is seen to be necessary,” he said. “Mass population-based vaccination in the UK should now end.”
The Covid modellers at Imperial College have begun to back down. About time too. Over the past few weeks, they have made extreme claims about the omicron variant that cannot be fully justified by fundamental science, let alone by clinical observation.
Dr. Peter A. McCullough, MD, MPH, is a board-certified cardiologist who has testified before committees of the US and Texas Senate regarding the treatment of COVID-19 and management of the ongoing pandemic.