Long-term vaccine protection of kidney transplant recipients against SARS-CoV2 variants depends on cellular humoral memory
ESPI M. 1,2, CHARMETANT X. 1,3, BENOTMANE I. 4, GALLAIS F. 5, MORELON E. 1,3, FAFI-KREMER S. 5, CAILLARD S. 4, THAUNAT O. 1,3
1 CIRI, INSERM U1111, Team 'Normal and pathogenic B cell responses', Lyon, France; 2 Department of nephrology, Lyon Sud university Hospital, Hospices Civiles de Lyon, Lyon, France; 3 Department of transplantation, Hospices civiles de Lyon, Lyon, France; 4 Department of nephrology and transplantation, Strasbourg university Hospital, Strasbourg, France; 5 Department of virology, Strasbourg university Hospital, Strasbourg, France
Background: We have shown that immediate vaccine protection of kidney transplant recipients (KTR) against COVID-19 depends on neutralizing antibodies (NAbs). As a result of declining NAbs titres and the emergence of viral variants, many vaccine-responders lose their serological protection over time. What risk are they exposed to?
Methods and results: The severity of infections with the Omicron variant was compared in 182 vaccinated KTR according to i) their peak anti-Wuhan NAbs, and ii) the level of anti-BA.1 NAbs just before infection. No (0/18) vaccine responder KTR who retained a neutralizing titer of anti-BA.1 NAbs were hospitalized, compared with 27% (28/104) of non-responders. Of the 60 initial vaccine responders who no longer had NAbs at the time of BA.1 infection, only 5/60 (8%) were hospitalized, suggesting the existence of a NAbs-independent protection.
To identify the immunological mechanisms involved, Wuhan (vaccine strain) and BA.1 virus-specific immune effectors were measured at peak and ≈6 months post-vaccination in 33 never-infected vaccinated KTR. An anti-Wuhan pseudo-neutralization test was used to identify responders at peak. While after 6 months, only 8/27 (30%) of responders still had seroneutralizing antibody titers against BA.1, 20/27 (74%) still possessed anti-BA.1 memory B cells in ELISPOT. Their characterization by cytometry demonstrated that these memory B cells i) derived from a germinal center reaction, and ii) recognized epitopes conserved between Wuhan and BA.1.
Conclusion: Unlike serological memory which wane overtime, humoral cellular memory, generated during the same post-vaccination response, persists, and its cross-reactivity offers long-term protection to KTR, including against viral variants. These results suggest that it is probably possible to space out anti-SARS CoV2 booster vaccinations in KTR.