Third vaccine dose increases immune response to 68% in French transplant recipients
Simon Collins, HIV i-Base
A higher percentage of people on immunosuppressive treatment due to solid organ transplants showed increased immune responses to a third dose of the Pfizer mRNA vaccine against COVID-19. Despite these improvements, more than 30% still showed no detectable antibody responses, with a need for continued caution.
This was a retrospective analysis from a cohort group of 101 transplant recipients (78 kidney, 12 liver, 8 lung or heart, and 3 pancreas). Mean age was 58 (SD: +/– 2) and 69% were men and average time since the transplant was about eight years. The results were published in a letter to the NEJM. 
Immunosuppressive treatment included glucocorticoids (in 87% of patients), calcineurin inhibitors (in 79%), mycophenolic acid (in 63%), mammalian target of rapamycin inhibitors (in 30%), and belatacept (in 12%).
The first two doses were given one month apart with the third dose approximately two months later.
The percentage of people with antibody responses to SARS-CoV-2 steadily increased from 0% before the first dose to 4%, 40% and 68% after each of the three doses respectively. See Table 1.
Table 1: Percentage of antibody responses 4 weeks after injections
|Baseline||0%||0 to 4|
|After dose 1||4%||1 to 10|
|After dose 2||40%||31 to 51|
|After dose 3||68%||58 to 77|
The third dose generated new antibody responses in 26/59 (44%) people with no responses after the second dose. Strength of antibody titres in the 40 people with responses after the second dose from 36±12 before the third dose to 2676±350 1 month after the third dose (p<0.001).
Factors linked to lack of response to the third dose included older age, greater immune suppression and lower eGFR. However, this cohort was still relatively young with good CD4 counts, although eGFR showed more serious kidney function. 
Mean age was 54 (+/– 2) vs 65 years (+/–3), p<0.001; CD4 T cell count was 529 (+/– 37) vs 339 cells/mm3 (+/–38) (p=0.002); and eGFR was 60 +/– 3 vs 45 mL/min/1.73m2 (+/–4), p=0.005; in the responders vs non responders respectively.
No serious events were reported from the third dose.
Despite the positive results, the authors still cautioned the importance of maintaining barrier protection and encouraging vaccination of relatives given the relatively high percentage of people who still didn’t develop antibody responses.
These results are important for supporting use of a third vaccine dose in people who are unlikely to generate immune responses to a two-dose schedule.
This is even though the vaccine might be generating cellular immunity that was not measured in the study.
Even without knowing titre levels needed for protection, the chance test to check individual immune responses in the small percentage of HIV positive people in this situation would be helpful. The results are likely to affect individual decisions about relaxing lock down and have a similar impact on improving their quality of life.
- Kamar N et al. Three doses of an mRNA COVID-19 vaccine in solid-organ transplant recipients. NEJM, correspondence. DOI: 10.1056/NEJMc2108861. (23 June 2021).
- Supplementary appendix.
This article was first published on 24 June 2021.