ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Immunogenicity of COVID-19 vaccines in kidney transplant recipients and their close household contacts (#173)

Griffith Perkins 1 2 , Matthew Tunbridge 2 , Cheng Sheng Chai 1 , Tania Salehi 2 , Arthur Yeow 3 4 , Christopher Hope 3 5 6 , Svjetlana Kireta 2 3 , Christopher Drogemuller 2 3 , Alistair Porter 1 , Pablo Valtanen 3 4 , Plinio Hurtado 2 3 , Steve Chadban 7 , Simon Barry 3 5 6 , Pravin Hissaria 1 2 , Branka Grubor-Bauk 3 4 , Toby Coates 2 3
  1. University of Adelaide, Adelaide, SA, Australia
  2. Central Adelaide Local Health Network, Adelaide, SA, Australia
  3. University of Adelaide, Adelaide, SA, Australia
  4. Basil Hetzel Institute, Adelaide, SA, Australia
  5. Robinson Research Institute, Adelaide, SA, Australia
  6. Women's and Children's Hospital, Adelaide, SA, Australia
  7. Royal Prince Alfred Hospital, Camperdown, NSW, Australia

BACKGROUND: The COVID-19 mortality rate amongst kidney transplant recipients (KTR) is 24%,(1) 7 times higher than in the general population. Because of this, transplant recipients were given priority status for vaccination in Australia. However, vaccine efficacy in this group is questioned due to the use immunosuppressive medications.  AIM: To compare COVID-19 vaccine (BNT162b2 and ChAdOx1) immunogenicity in KTRs with that of their cohabitants, with a focus on correlates of protection from infection,(2) in order to inform policy for the roll-out of booster vaccines.  RESULTS/DISCUSSION: 43% of KTRs [12/28] produced anti-SARS-CoV-2 spike IgG after 2 vaccine doses (compared with 100% of cohabitants [32/32]). However, the median antibody titre for KTRs who did seroconvert was 151-fold lower than that of their cohabitants. Concordantly, KTRs had a heavily reduced capacity for virus neutralisation; even patients with promising antibody titres failed to effectively inhibit viral entry into ACE2+ cells. With respect to cellular immunity, we found that KTRs had, on average, 10-fold fewer spike-reactive IFNg-secreting cells following 2 vaccine doses, with the exception of patients receiving rapamycin. KTRs taking rapamycin (n=4) had higher antibody titres and a 28-fold greater frequency of spike-reactive IFNg-secreting cells compared with KTRs receiving standard of care triple therapy. Concordantly, activation-induced marker expression revealed KTRs receiving rapamycin to have significantly higher frequencies of spike-reactive CD4+ (4-1BB+OX40+) and CD8+ (4-1BB+CD69+) T cells compared with healthy cohabitants and other KTRs.  CONCLUSION: KTRs display poor humoral and cellular immunity to the COVID-19 vaccines that are available in Australia. By contrast, their cohabitants demonstrate robust immune correlates of protection from infection and transmission. We recommend priority vaccination of close household contacts of KTRs, and have initiated a randomised controlled trial to test modification of immunosuppression with rapamycin as an adjuvant therapy to improve vaccine responses in this vulnerable group.

  1. Phanish M, Ster IC, Ghazanfar A, Cole N, Quan V, Hull R, Banerjee D. Systematic review and meta-analysis of COVID-19 and kidney transplant recipients, the South West London Kidney Transplant Network experience. Kidney international reports. 2020 Dec 19.
  2. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, Subbarao K, Kent SJ, Triccas JA, Davenport MP. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature medicine. 2021 May 17:1-7.