Immunocompromised patients experience a less response to SARS/CoV-2 mRNA vaccinations

The coronavirus disease of 2019 (COVID-19) has posed the biggest threat to ‘at-risk people, such as people who are elderly, chemotherapy patients or those with a compromised immune system. While in certain countries, mass vaccination schemes as well as repurposed drugs and monoclonal antibodies are starting to slow the progression of the disease but there are concerns.

SARS-CoV-2 variants that are of concern, such the Delta variant, have been shown to infect people who have been vaccinated , and are still transmissible. To study the protection offered to immunocompromised individuals through messenger ribonucleic acid (mRNA) vaccines, researchers from the University of Pennsylvania explore the germinal cell responses in both healthy individuals and kidney transplant patients in their latest study that was published on the preprint server medRxiv*.

Study: Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised people. Image Credit: ustas7777777 /

An overview on the mRNA vaccine technology

The mRNA vaccines deliver the virus’mRNA to the person who has been vaccinated. By this method the mRNA, that encodes for specific epitopes relies on the host cell machinery to express these epitopes. These antigens can then be recognized by the immune system, without any threat of infection.

Memory B-cells can rapidly create antibody-secreting plasma cells. Both memory B-cells and plasma cells that secrete antibody are produced during germinal center (GC) reactions in the lymph nodes.

In these reactions, B-cells that have been exposed to the pathogen go through somatic hypermutation to create B-cells with high affinity for specific antigens. They later differentiate into memory B cells or plasma cells. These GC reactions can be stimulated by mRNA vaccines. Unfortunately, these reactions are inhibited by immunocompromised patients.

About the study

The researchers of the current study employed a fine-needle aspirationprocedure, which involves the collection of a biopsy to gather small amounts of liquid to analyze samples and determine the GC responses to mRNA vaccines in healthy donors as well as kidney transplant patients. Two weeks after the first immunization , and eight days after that samples were collected from 15 patients.

Both doses of severe acute respiratory syndrome coronavirus 2 (2 (SARS-CoV-22) specific antibodies were significantly increased. Particularly, it was found that B-cells were capable of binding to both full spike proteins and the receptor binding domain (RBD) which is part of the spike protein’s S1 subunit. The RBD is essential to SARS-CoV-2 pathogenicity, as it binds to angiotensin-converting enzyme 2 (ACE2) receptor to allow viral entry to the cell.

However similar results could not be seen in kidney transplant patients. The scientists were able to find 13 people who initially had consented to participate in the study. One withdrew consent and two more dropped out due to failure to collect samples and insufficient cells for analysis.

The patients had a slower rate of cell recovery and large numbers of B-cells were absent. Although researchers did find small amounts of anti-SARS-CoV-2-B-cells in the patient population following vaccination however, it was not enough to provide protection.

There was a complete failure of GC B-cell responses. Memory cells that protect against SARS-CoV-2 were discovered; however, they were insufficient to provide adequate immunity. The T-cell responses were also weak and this is a different aspect that hasn’t been observed in patients with health issues.


The authors stress the importance of their findings in relation to patients suffering from immunocompromised diseases and those taking immunosuppressant medication. The suboptimal vaccine response is confirmed by studies that study earlier vaccines for viruses such as influenza.

This study could prove useful in forming public health policy, specifically the policies for nursing homes where immunocompromised patients are likely to be found. As restrictions are lifting the patients are increasing susceptible to infection, especially since the boundaries for population immunity against the Delta variant are much greater than the original strain found in Wuhan.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behaviour, or treated as established information.

Journal reference:

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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