Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

Abstract

It is critical to protect immunocompromised patients against COVID-19 with effective SARS-CoV-2 vaccination as they have an increased risk of developing severe disease. This is challenging, however, since effective mRNA vaccination requires the successful cooperation of several components of the innate and adaptive immune systems, both of which can be severely affected/deficient in immunocompromised people. In this article, we first review current knowledge on the immunobiology of SARS-COV-2 mRNA vaccination in animal models and in healthy humans. Next, we summarize data from early trials of SARS-COV-2 mRNA vaccination in patients with secondary or primary immunodeficiency. These early clinical trials identified common predictors of lower response to the vaccine such as anti-CD19, anti-CD20 or anti-CD38 therapies, low (naive) CD4+ T-cell counts, genetic or therapeutic Bruton tyrosine kinase deficiency, treatment with antimetabolites, CTLA4 agonists or JAK inhibitors, and vaccination with BNT162b2 versus mRNA1273 vaccine. Finally, we review the first data on third dose mRNA vaccine administration in immunocompromised patients and discuss recent strategies of temporarily holding/pausing immunosuppressive medication during vaccination.

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study

“…While studies have shown immune responses in some immunocompromised individuals after 2 doses of an mRNA vaccine [22] , others have reported immune responses in substantially fewer individuals with immune deficiency after 2 doses compared with healthy individuals [23] . Earlier immunogenicity studies reported lower seroconversion rates after COVID-19 vaccination in immunocompromised patients, compared to immunocompetent individuals [11] .…”

“…Finally, both allogeneic HSCT and anti-CD20 therapy have been associated with increased duration of viral shedding and COVID-19 relapses, which are linked to virus replication and mutation [39] , [40] . Further, although early administration of COVID-19 monoclonal antibody (mAb) treatment can improve COVID-19 outcomes of immunosuppressed individuals infected with SARS-CoV-2 [22] , mAb can also lead to selection of mAb resistant variants [41] . As such, COVID-19 vaccines remain critical to provide adequate protection for these populations.…”

“…Additionally, individuals with moderate-to-severe immunosuppression are not a homogeneous group with regards to VE, and severity of the immunocompromising condition could have an impact on VE. Indeed, VE (3 or 2-dose vaccinated vs unvaccinated) has been reported to vary considerably among specific immunocompromising subgroups [22] , [23] , [24] , [42] , [43] , with lower VE linked to more severe immunosuppression compared to less severe immunosuppression [12] , [23] . In our work, the rVE of 3 doses vs 2 doses was consistent across subgroups of immunocompromising conditions.…”

Convalescent plasma therapy in immunocompromised patients infected with the BA.1 or BA.2 Omicron SARS-CoV-2

“…Immunocompromised patients are at high risk of severe COVID-19. Since they might not elicit an adequate immune response after vaccination, passive immunization using ex-vivo produced neutralizing antibodies is one of the key therapeutic options in such populations 1 . Monoclonal anti-spike antibodies have shown a great risk reduction of hospitalization or death in immunocompetent patients 2,3 .…”

Self-Reported Use of COVID-19 Immunologic Test Results to Inform Decisions About Daily Activities and COVID-19 Vaccination

“…However, utility of these antibody-based tests may be reduced in some individuals due to low or absent antibody titers [9][10][11][12]. Furthermore, serologic testing is not informative for some patients, such as those undergoing iatrogenic B-cell depletion or with primary humoral immunodeficiencies [13,14].…”