A third COVID-19 vaccine dose in kidney transplant recipients induces antibody response to vaccine and Omicron variants but shows limited Ig subclass switching
Authors: Lee Jenny M. , Sachithanandham Jaiprasath , Lee John S. , Shapiro Janna R. , Li Maggie , Sitaris Ioannis , Peralta Stephanie R. , Wouters Camille , Cox Andrea L. , Segev Dorry L. , Durand Christine M. , Robien Mark , Tobian Aaron A. R. , Karaba Andrew H. , Blankson Joel N. , Werbel William A. , Pekosz Andrew , Klein Sabra L. 
Published: January 2025

ABSTRACT

Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as two Omicron variants BA.1 and BA.5 were investigated and compared with healthy controls who also received a third dose of mRNA vaccine (HCs). Total IgG and live virus neutralizing antibody titers were reduced in KTRs compared with controls for all variants. KTRs displayed altered IgG subclass switching, with significantly lower IgG3 antibodies. Responses in KTRs were also very heterogeneous, with some individuals showing strong responses but a significant number showing no Omicron-specific neutralizing antibodies. Taken together, immune responses after COVID-19 vaccination in KTRs were not only lower than HCs but highly variable, indicating that simply increasing the number of vaccine doses alone may not be sufficient to provide greater protection in this population. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations, such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.

IMPORTANCE
This study addresses the challenges faced by kidney transplant recipients (KTRs) in mounting effective immune responses against COVID-19. By evaluating the antibody responses to a third dose of monovalent mRNA COVID-19 vaccine and its effectiveness against Omicron subvariants (BA.1 and BA.5), this study reveals significant reductions in both binding and neutralizing antibodies in KTRs compared with healthy controls. The research highlights altered IgG subclass switching and heterogeneous responses within the KTR population. Reduced recognition of variants, coupled with differences in IgG subclasses, decreases both the quality and quantity of protective antibodies after vaccination in KTRs. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations, such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.