Authors’ Reply: SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?
Authors: Eva Schrezenmeier, Arne Sattler, Fabian Halleck, Klemens Budde
Journal: Journal of the American Society of Nephrology (2022)

We appreciate the comment of Wijtvliet and colleagues and fully agree that low efficacy of coronavirus disease 2019 vaccinations in kidney transplant recipients (KTRs) represents a major problem and that new vaccination strategies are urgently needed. Intradermal application of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines is an interesting approach because first data from healthy adults suggest robust serological response at lower doses.1 However, limitations of the intradermal delivery trial are the small sample size and the lack of analysis of the cellular immune response. Therefore, broader clinical studies in healthy individuals and KTRs are necessary to assess long-term clinical efficacy. Thus, much more data are needed to recommend intradermal application of mRNA-based vaccines against SARS-CoV-2. The intriguing pathophysiologic idea behind the preliminary report in medRxiv that Wijtvliet et al. reference is that more antigen-presenting cells reside in the skin than in skeletal muscle,2 thereby raising a stronger vaccine response with a lower dose. Although previous data from influenza vaccination suggest a better response of intradermal application in KTRs, it is not clear how the data can translate to mRNA vaccines, which elicit an excellent immediate immune response in most individuals. Our data demonstrate that KTRs develop high frequencies of antigen-specific CD4 cells after vaccination, suggesting successful antigen presentation. In KTRs the mature immune response, which requires cellular proliferation and a complex interplay among immune cells, seems to be blocked by immunosuppressants. To directly address this problem, we have very recently described excellent efficacy of a fourth dose of the mRNA vaccine BNT162B2 in 29 KTRs without previous immune response under a temporary (5 weeks) hold of mycophenolate (MPA). Seroconversion rate (anti-S1-IgG and neutralizing antibodies) was 84% after 1 month and we saw a rapid increase in antigen-specific peripheral B cells.3 As expected, kidney function remained unchanged because several previous studies have demonstrated the safety of this intervention and MPA cessation is standard for women who want to become pregnant.4 The temporary hold of MPA under adequate treatment with calcineurin inhibitor plus corticosteroids, together with close surveillance, might be the most feasible and fastest way to achieve adequate protection for KTRs, especially in light of emerging new variants. We agree that intradermal application of a reduced dose would be one way to improve worldwide accessibility to the vaccines, especially in the face of production shortages or high costs. However, KTRs represent a very small, yet highly vulnerable, patient cohort that, despite repeated vaccination, do not contribute substantially to global misdistribution of vaccines. Disclosures K. Budde reports consultancy with Abbvie, Alexion, Astellas, Bristol-Myers Squibb, Chiesi, CSL Behring, Fresenius, Hansa, Hexal, MSD, Novartis, Otsuka, Pfizer, Quark, Roche, Sandoz, Shire, Stada, Veloxis, Vifor, and Vitaeris; research funding from Abbvie, Alexion, Astellas, Bristol-Myers Squibb, Chiesi, CSL Behring, Fresenius, Hansa, Hexal, MSD, Novartis, Otsuka, Pfizer, Quark, Roche, Sandoz, Shire, Veloxis, Vifor, and Vitaeris; honoraria from Abbvie, Alexion, Astellas, Bristol-Myers Squibb, Chiesi, Fresenius, Hexal, Novartis, Otsuka, Pfizer, Quark, Roche, Sandoz, Shire, Stada, and Veloxis; and advisory or leadership role with Astellas, Bristol-Myers Squibb, Chiesi, Hansa, Hexal, MSD, Novartis, Pfizer, Roche, and Veloxis. F. Halleck reports honoraria with MSD and Novartis. All remaining authors have nothing to disclose. Funding None.