Hyper... hypervaccinated! Is there a vaccination limit for COVID-19?

A German man made headlines after receiving 217 COVID-19 vaccinations. Could it give super immunity? Or are these cases damaging the immune system?

A hypervaccinated man received a 217th vaccination for science

The man in question was 62 years old at the time of the study. He had received 217 vaccinations against SARS-CoV-2 within 29 months, with the 217th vaccination being administered by the research team after approval by the ethics committee. The hypervaccination took place outside of a clinical trial context and was carried out contrary to national vaccination recommendations. The eight different vaccines available, including mRNA vaccines, were used. Even before the study began, the Magdeburg (Germany) resident had several blood tests carried out, which the research team was able to draw on.1

The hypervaccinated man enters the media spotlight

The research team became aware of this case through the media, and contacted him to take a closer look at the immunological consequences of his hypervaccination. However, they were not the only ones to focus intensively on his story. The Magdeburg public prosecutor's office launched an investigation into the case, alleging fraud. He is suspected of having sold vaccination certificates to people who refused to be vaccinated against COVID-19.1,2

The hypervaccinated man doesn't give COVID a chance

The patient showed no vaccine-related side effects. In the period from November 2019 to October 2023, 62 routine clinical-chemical parameters were recorded. Again, no abnormalities attributable to hypervaccination were recognisable. Further examinations did not reveal any signs of a previous SARS-CoV-2 infection. The SARS-CoV-2 antigen tests, PCRs and nucleocapsid serology were repeatedly negative.1

What does the anti-spike SARS-CoV-2 IgG level tell us about hypervaccination?

The anti-spike SARS-CoV-2 IgG level was measured before the 214th vaccination and repeated at different times. The highest levels were found on the day of the 214th vaccination and on the 3rd day after the 215th vaccination. However, the comparison with a reference cohort of 29 vaccinated persons (55 % female, 45 % male), which served as a control group, yielded sobering results. The contraction kinetics corresponded to those of the control group. The 217th vaccination only led to a slight increase in anti-spike IgG values.1

Unusual IgG subclass switch to IgG4 due to repeated SARS-CoV-2 mRNA vaccinations

Repeated administration of SARS-CoV-2 mRNA vaccinations can result in an unusual IgG subclass switch to IgG4. On the 189th day after the 215th vaccination, the anti-spike IgG4 antibodies of the hypervaccinated man were elevated in absolute numbers but not in relative frequencies (compared to control subjects on day 189 after their third vaccination).1

Anti-spike IgG in the saliva of the hypervaccinated patient, and a convincing serum neutralisation capacity

A slight increase in anti-spike IgM and IgA values was measured in the serum of the hypervaccinated patient compared to the control group. Interestingly, in contrast to the control group, anti-spike IgG was detectable in the saliva of the hypervaccinated patient. Compared to the control group, the hypervaccinated patients had a higher serum neutralisation capacity for wild-type and Omicron B1.1.529 spike proteins (5-4 and 11-5 times higher respectively).1

A higher peptide sensitivity due to hypervaccination

In hypervaccinated patients, CD8+ T cells specific for the immunodominant spike epitope HLA-A*01/LTD were present 6 times more frequently than in the control group on day 189 after the 215th vaccination. The 217th vaccination enhanced this immune response. There was evidence of a higher absolute number of epitope-specific CD8+ effector memory and effector T cells in hypervaccinated patients: After epitope-specific stimulation, more cytokine-positive cells had been measurable in the hypervaccinated than in the control subjects.

The CD8+ T cells of the hypervaccinated patients showed a higher peptide sensitivity compared to the control group. Analysis of the spike-reactive CD4+ T cells confirmed the absence of nucleocapsid-specific immunity. It showed similar levels of cytokine-producing CD4+ T cells in the hypervaccinated compared to the control group. However, the hypervaccinated patient had a higher peptide sensitivity than the control group.1

COVID-19: There are no such things as too many vaccinations

The research group was thus able to show that

SARS-CoV-2 hypervaccination

  1. Kocher K. et al. (2024). Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual. Lancet Infect Dis. 2024 Mar 4:S1473-3099(24)00134-8. 
  2. https://www.theguardian.com/society/2024/mar/06/hypervaccinated-man-217-covid-jabs-no-side-effects-germany