Do kidney transplant recipients need a third booster dose of mRNA COVID-19 vaccine?

Transplant patients are always on immunosuppressive drugs to reduce their chances of contracting graft rejection on receiving a transplant. This is why all transplant patients are at an increased risk of contracting all forms of infection and need strict monitoring.

Kidney transplant recipients (KTRs) thus experience a high risk of infection with the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the virus that causes coronavirus disease 2019 (COVID-19). The KTR population has therefore been prioritized for vaccination.

A team of researchers in France have observed that the “standard” 2 dose regimen for mRNA COVID-19 vaccines could provide adequate protection to only a few KTRs. It has also been shown in multiple studies that a considerable population of vaccinated KTRs were easily infected with SARS-CoV-2.

The researchers conducted a prospective, observational study and explained the serological markers responsible for detecting the appropriate KTR population to administer a third dose of the mRNA vaccines.

Study: Predictive factors of response to 3rd dose of COVID-19 mRNA vaccine in kidney transplant recipients. Image Credit: LookerStudio / Shutterstock

A preprint version of the study, which is yet to undergo peer review, is available on the medRxiv* server.

How were the effects of the third dose of mRNA vaccines monitored?

The benchmark for COVID-19 specific antibodies – IgG antibodies directed against the Receptor Binding Domain (RBD) of the spike glycoprotein of the SARS-CoV-2, anti-RBD IgG – is 142 BAU/mL (binding arbitrary units/mL) as per the World Health Organization (WHO).

Kidney transplant recipients having a lower number of antibodies after 14 days of their second dose of the Pfizer BioNTech COVID-19 vaccine were identified using standard laboratory assays. These tests involved detecting levels of Anti-RBD IgG (marker of humoral immunity), interferon-γ (a pro-inflammatory cytokine), and spike protein-specific CD4+ T cells (also known as Helper cells, markers of cellular immunity) in their bloodstream.

These patients then received a third dose of the Pfizer/BioNTech mRNA vaccine. Following this, the antibody titers were measured again using chemiluminescent assays.

What were the main observations made?

The researchers observed that 42% of patients showed a high response rate (89%) to the third dose, (antibody levels reaching beyond 142 BAU/mL), with the younger patients (in their 40s) responding better than the elderly counterparts (aged 50 and above). The response was variable among individuals. The most severe adverse effect was fever <39°C for two days and pain at the site of injection.

Another important observation made in the study was that low titers of both anti-RBD IgG as well as CD4+ T cells were crucial for the third dose to be effective in inducing an adequate immune response. These could be possible serological markers for identifying patients needing a third dose of the mRNA vaccines.

Those patients with inadequate levels of either marker, or both, showed considerably lower response rates (72% for those only positive for low anti-RBD IgG, 56% for those positive for only low levels of spike-specific CD4+ T cells, and a meager 7% for those negative for both).

Implications of this study

This was a pilot study involving 66 patients upon whom the effects of a third dose of vaccine were observed. Although this study is yet to be reviewed, it provides valuable insights on the assessment of patients for a possible third booster dose of an mRNA vaccine.

Two valuable serological markers for considering kidney transplant patients for the third dose of vaccine are:

1. Low levels of anti-RBD IgG antibody (specific to SARS-CoV-2 spike proteins)
2. Low levels of spike-specific Helper CD4+ T cells

For patients who do not show adequate markers for a third dose, it would be best to provide passive immunization using anti-SARS-CoV-2 monoclonal antibodies, as suggested in other studies involving vulnerable patient populations.

*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 behavior, or treated as established information.

Written by

Sreetama Dutt

Sreetama Dutt has completed her B.Tech. in Biotechnology from SRM University in Chennai, India and holds an M.Sc. in Medical Microbiology from the University of Manchester, UK. Initially decided upon building her career in laboratory-based research, medical writing and communications happened to catch her when she least expected it. Of course, nothing is a coincidence.