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Comparative immunogenicity of heterologous versus homologous 3rd SARS-CoV-2 vaccine doses in kidney transplant recipients

by Tina Thomson, Maria Prendecki, Sarah Gleeson, Paul Martin, Katrina Spensley, Charlotte Seneschall, Jaslyn Gan, Candice L. Clarke, Shanice Lewis, Graham Pickard, David Thomas, Stephen P. McAdoo, Liz Lightstone, Alison Cox, Peter Kelleher, and Michelle Willicombe

Posted: January 26, 2022
Server: medRxiv
DOI: 10.1101/2022.01.25.22269778

Background

Solid organ transplant recipients have attenuated immune responses to SARS-CoV-2 vaccines. Emerging evidence suggests at least equivalent immunogenicity of heterologous compared with homologous vaccine regimens in the general population. In this study, we report on immune responses to 3^rd dose BNT162b2 vaccines in transplant recipients either primed with ChAdOx1 or BNT162b2.

Methods

700 kidney transplant recipients were prospectively screened for serological responses (median time of 33 (21-52) days) following 3 primary doses of a SARS-CoV2 vaccine. All vaccine doses were received post-transplant, and all 3^rd doses were BNT162b2. All participants had serological testing performed post-2^nd vaccination at a median time of 34 (IQR 26-46) days following the 2^nd inoculation, and at least once prior to their 1^st dose of vaccine.

Results

366/700 (52.3%) participants were primed with BNT162b2, whilst 334/700 (47.7) had received ChAdOx1. Overall, 139/700 (19.9%) participants had evidence of prior infection. Of 561 infection naïve participants, 263 (46.9%) had no detectable anti-S following 2-doses of vaccine (V2). 134 (23.9%) participants remained seronegative post 3^rd vaccine (V3); 54/291 (18.6%) and 79/270 (29.3%) of participants receiving BNT162b2 and ChAdOx1 respectively, p=0.0029. Median anti-S concentrations were significantly higher post-V3 in patients who had received BNT162b2 compared with ChAdOx1, at 612 (27-234) versus 122 (7.1-1111) BAU/ml respectively, p<0.0001.

Cellular responses were investigated in 30 infection naïve participants at a median time of 35 (24-46) days post-V3. Eighteen of 30 (60.0%) participants had undetectable T-cell responses. There were neither qualitative or quantitative differences in T-cell responses between those patients who received BNT162b2 or ChAdOx1 as their first 2-doses, with 10/16 (62.5%) and 8/14 (57.1%) respectively having undetectable T-cell responses, p=0.77.

Conclusion

A significant proportion of transplant recipients remain seronegative following 3 doses of SARS-CoV-2 vaccines, with anti-S concentrations lower in patients receiving heterologous versus homologous vaccinations.

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