Boosting Immunity, Boosting Risk? The Surprising Link Between IgG4 and COVID Breakthrough Infections

Post-Vaccination IgG4 and IgG2 Class Switching is linked to Increased Risk of SARS-CoV-2 Infections

A new study published in Infectious Disease Practice has revealed a concerning correlation between the class switching of antibodies after COVID-19 mRNA booster vaccinations and a heightened risk of breakthrough infections. Specifically, the study found that elevated levels of IgG4 and IgG2 antibodies, which increase significantly following the third mRNA dose, are linked to an increased risk of symptomatic SARS-CoV-2 infections. 

The study analyzed a longitudinal subset of 83 healthcare workers who received three doses of the COVID-19 vaccine. Additionally, they included 66 healthcare workers from the same cohorts who were analyzed at a specific timepoint (T9) corresponding to May 2022, four months after the first booster vaccination.

The study, conducted by a team of researchers from Spain, tracked the immune responses of healthcare workers over nearly three years. They observed that the levels of IgG4, a subclass of antibodies that does not mediate strong immune responses compared to other subclasses like IgG1, rose sharply after the first booster dose. This shift, marked by an increase in non-cytophilic antibodies (IgG4 and IgG2) relative to cytophilic antibodies (IgG1 and IgG3), was found to correlate with a reduced ability to neutralize the virus, thus lowering the effectiveness of the immune response.

Interestingly, although IgG4 and IgG2 were associated with a higher risk of breakthrough infections, the study suggests that these antibodies may still play a role in preventing severe disease. Their reduced immune-activating properties could help mitigate inflammation and other harmful effects during infection. However, the findings emphasize the need for further investigation into the long-term impacts of repeated mRNA vaccinations on immunity and how vaccination strategies might be adjusted to optimize protection.

The study’s conclusions underscore the complexity of the immune response to COVID-19 vaccines and the potential need for re-evaluating booster schedules and vaccine formulations. As researchers continue to explore the balance between vaccine-induced protection and immune function, these findings could influence future mRNA vaccine development and booster administration, not only for SARS-CoV-2 but for other infectious diseases as well.


REFERENCES

  1. Pérez, Carla Martín et al. Post-vaccination IgG4 and IgG2 class switch associates with increased risk of SARS-CoV-2 infections Journal of Infection, Volume 0, Issue 0, 106473

  2. Irrgang P, Gerling J, Kocher K, Lapuente D, Steininger P, Habenicht K, Wytopil M, Beileke S, Schäfer S, Zhong J, Ssebyatika G. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Science immunology. 2022 Dec 22;8(79):eade2798.
  3. Irrgang P, Gerling J, Kocher K, Lapuente D, Steininger P, Habenicht K, Wytopil M, Beileke S, Schäfer S, Zhong J, Ssebyatika G. Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Science immunology. 2022 Dec 22;8(79):eade2798.

Comments

Post a Comment

Popular posts from this blog

A New Onset of Ulcerative Colitis post-2nd-breakthrough-COVID-19

Image
A 21-year-old non-smoking Caucasian male with a history of acute pancreatitis but no other medical issues or family history had two doses of the BNT162b2 mRNA COVID-19 vaccine.  Four months after the second dose he had his first episode of COVID-19. Although not hypoxic, he felt pretty unwell for a week, with a severe cough, fever, generalized body ache, headache, and loss of taste. He received the third dose of the vaccine two months after recovering from COVID. Nine months after the third dose, he had the second episode of COVID-19, during which he was mildly unwell for three days, recovered, and did not require any anti-viral medication or antibiotics. One week post the second episode of COVID-19, he developed diarrhea and abdominal pain. It then progressed to bloody diarrhea. Ulcerative colitis was diagnosed based on his clinical symptoms, biopsy changes, and the exclusion of other causes.  There are ten published case reports about the newly diagnosed ulcerative colitis ...
Read more

Wave X

Image
From wild type to Alpha (B.1.1.7), Delta (B.1.617.2), Omicron BA.1, BA.2, BA.5,  BQ.1/BA.2.75,  XBB, JN.1, FLiRT variants and now XEC and LP.8.1 (BA.2.86.1), the virus keeps evolving, continuously demonstrating its ability to adapt and mutate.  As we enter the tenth wave of COVID-19 in the U.S, the XEC variant has emerged as the dominant strain - in line with expectations. It could be " a weak leading variant "  but will it be a " very muted holiday wave relative to all prior years , due to weak evolution and large summer numbers"?  Until recently in the US KP.3.1.1 was dominating wastewater samples and accounting for a considerable proportion of infections. Looking at the growth advantages of variants over the last year led to predictions of significantly lower impact  than JN.1 that "XEC should only modestly bump what the winter wave would be without any new variant" by one of COVID forecasters . But other variants are also gaining traction. The off...
Read more

Crossroads of Pathogens: The Evolving Threat of Avian Influenza

Image
Influenza viruses are infamous for their ability to mutate and adapt, making the study of their evolution critical for public health. Some like H5N1 are severe, others as H7N3 are typically present with mild symptoms. The classification of influenza subtypes relies on the hemagglutinin (H) and neuraminidase (N) proteins on the viral surface, with 18 H subtypes and 11 N subtypes combining into diverse influenza strains. While most pose limited risks to humans, certain mutations can significantly alter their behavior. Case 1: Mutated H5N1 in a Vancouver Teen Canadian teen, who lives in the Fraser Health Region of British Columbia, first developed symptoms on Nov. 2 and was tested on Nov. 8, with a positive result confirmed on Nov. 9.  It was the first positive case of bird flu detected in a human in Canada. The teenager, hospitalized with a mutated H5N1 strain, was unconscious for over two weeks. The teen has made progress and is expected to recover. Alarmingly, this strain exhibits ...
Read more