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.

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.

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