Third dose of mRNA vaccine improves antibody responses in kidney transplant recipients

Simon Collins, HIV i-Base

On 23 July 2021, a research letter in JAMA reported that a third vaccine effectively increase antibody response in 49% of kidney transplant recipients who had no or minimal antibody levels after the second dose.

Results were from University Hospital Strasbourg, following the early French recommendation to use a third vaccine

The included 159 kidney transplant recipients. The median age was 57 years (IQR: 49 to 66), 61% were men, and the median time from transplantation was 5.3 years (IQR, 1.9 to 11.1).

The definition of suboptimal response was IgG antibody levels > 50 arbitrary units/mL

At baseline (median 51 days, IQR: 48 to 59), 64/159 participants had antibody levels between 6.8 to 49.0 AU/mL and 95/159 had antibody levels below the test sensitivity limit (test range: <6.8 to 80,000 AU/mL).

After the third dose, measured after a median 28 days (IQR: 27 to 33 days), 78/159 (49%) had levels >50 AU/mL (median 586; IQR: 197.2 to 1920.1 AU/mL).

In multivariate analysis, only baseline antibody levels and use of triple immunosuppressant therapy (tacrolimus + MMF/MPA + steroids) were significant predictors of responding >50 AU/mL (p=0.001 and p=0.006 respectively).

Importantly, 27% of people with baseline responses <6.8 AU/mL responded to >50 AU/mL (compared to 81% of those who started at 6.8 to 49.9 AU/mL).

comment

These results support offering a third vaccine dose to previous non-responders, similar to other studies reported last month in the July issue of HTB. [2, 3]

They also show the urgency of finding alternative strategies for half of the group that still remain highly vulnerable to SARS-CoV-2.

Generating a response from those who started below the limit of detection perhaps suggests a fourth dose, perhaps with a different vaccine, might be important to study.

The UK has not yet published detailed plans for a potential third dose in September, but the rough details suggested this would not prioritise people based on previous antibody response.

The UK also apparently has no mechanism for people to access a third dose – and this should be urgently reviewed based on identifying non responders in the most vulnerable groups. This include those older than 80, people on immune suppressing treatment (for cancer or in transplant recipients), and HIV positive people with CD4 counts <50 cells/mm³.

References

1. Benotmane I et al. Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA. doi:10.1001/jama.2021.12339. (23 July 2021).
   https://jamanetwork.com/journals/jama/fullarticle/2782538
2. Third vaccine dose increases immune response to 68% in French transplant recipients. HTB (1 July 2021).
   https://i-base.info/htb/40812
3. Third COVID-19 vaccine dose in US cohort of people on immune-suppressing treatment: safety and ethical issues. HTB (1 July 2021).
   https://i-base.info/htb/40843

This report was first published on 25 July 2021.