Do patients with an impaired immune system have a good immune response to the corona vaccine? Will the vaccines protect them against COVID-19? During an international ZonMw webinar on 7 December 2021, researchers presented the first results from two studies: response to the corona vaccine in the case of kidney diseases and cancer.

The webinar began with a welcome from Dr. Daniël Warmerdam, programme manager at ZonMw, and a brief word of thanks from Marjolijn Sonnema, Director-General for Public Health at the Ministry of Health, Welfare and Sport. In December 2020, the Ministry commissioned ZonMw to fund investigation trialsstudying COVID-19 vaccination in different patient groups with impaired immune systems.

Modified vaccination strategy

Sonnema praised the researchers for having obtained results so quickly. As a result, the vaccination strategy for people with an impaired immune system could be adjusted at an early stage.

More frequent complications

The webinar was hosted by dr. Martijn Luijsterburg from Leiden University Medical Center, an expert in molecular biology and the area of the messenger molecule (mRNA) in mRNA vaccines. Luijsterburg took us back to the spring of 2021 when the first Dutch citizens were vaccinated against the SARS-CoV-2 virus, the causal agent of the COVID-19 (corona) disease. It was found that people with an impaired immune system had a higher chance of complications due to the illness.

Unique network

It prompted eight immune response studies after vaccination (immunogenicity) in people with a weakened or impaired immune systems. The safety of the vaccines in these patients is also being investigated. ‘Together, these eight studies form a unique network within which protocols and analytical methods were harmonised to facilitate comparisons between the studies’, said Luijsterburg.

RECOVAC study

The first speaker was researcher Jan-Stephan Sanders, an nephrologistat University Medical Center Groningen and principal investigator of the multicentre RECOVAC study. This study is investigating the immune response (humoral response) in patients with severe kidney failure, dialysis patients and kidney transplant recipients. The patients received two doses of the Moderna vaccine. Their blood was investigated at intervals for antibodies against the spike protein.

Transplanted kidney

In at least 99% of the patients, the researchers found antibodies after two doses of the vaccine. However, antibodies were only found in 57% of kidney transplant recipients. These patients had far fewer antibodies, and their antibodies were less capable of neutralising virus particles. The antibodies also disappeared from the blood more quickly.

Immunosuppressive medication

The primary cause of this ‘low or nonresponse’ is the use of the immunosuppressive drug MMF (Mycophenolate mofetil). This research demonstrated that two vaccinations are not sufficient for kidney transplant recipients.

T-cell response

Sanders also investigated the T-cell response (cellular response) in patients. These white blood cells also play a role in the immune system: they destroy infected cells and produce antibodies. Kidney transplant recipients and dialysis patients had significantly fewer T-cells than the control group after the second vaccination.

Alternative strategies

The majority of kidney transplant recipients and dialysis patients benefit from receiving three doses of the mRNA vaccine instead of the standard two doses. However, in the group of non-responders, a third vaccination has limited effect. Sanders: ‘We are investigating whether the vaccine will have an effect if we briefly stop administering MMF or if we administer a double dose of the vaccine. We are also investigating whether the Janssen vaccine is effective for these patients.’


Also read: Response to COVID-19 vaccines in the case of congenital immune disorders and haematological conditions
 

VOICE study

After several questions from the audience, it was the second speaker’s turn: Sjoukje Oosting, an oncologist at University Medical Centre Groningen. Together with colleagues from Erasmus MC and the Netherlands Cancer Institute, she is conducting the VOICE study in people with solid tumours. These are patients with skin, breast, bladder, intestinal or lung cancer, for example.

All patients produce antibodies against the virus

To what extent do chemotherapy, immunotherapy and chemo-immunotherapy influence the immune response among people with a tumour? And do they influence the safety of the vaccines? Oosting and her colleagues are investigating that in the prospective, multicentre VOICE study. At various time points, they measure the level of antibodies and T-cells against the coronavirus. Their findings: virtually all patients measured in the study, produce antibodies against the virus. This does not differ from the control group.

Antibodies are not always capable of neutralising the virus

However, these antibodies are not always capable of neutralising the virus. Oosting calculated the threshold value for this: 300 virus-binding antibodies per millilitre of blood. 6.9% of patients receiving immunotherapy did not achieve the threshold. For chemotherapy, that figure was 16.2%, 11.2% for chemo-immunotherapy. A third vaccination is probably helpful for this group of patients. That is being investigated in the VOICE study. On a positive note, no unexpected side effects of the vaccine were found.

Further investigations

The threshold value must be validated, Oosting said. Furthermore, the blood value decreases after a while. That has consequences for the vaccination strategy. Oosting: ‘We continue to collect data and will soon know more about our measurement point after six months.’

What is the next step?

A large proportion of the patients with cancer and kidney diseases responded well to COVID-19 vaccinations, but the studies will continue. In both studies. New results from the studies will be published on our webpage about research into the coronavirus.

Text: Riëtte Duynstee
Translation: Dave from NST Science

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