Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients

Abstract

Solid organ transplant recipients are at high risk of severe disease from COVID‐19. We assessed the immunogenicity of mRNA‐1273 vaccine using a combination of antibody testing, surrogate neutralization assays, and T cell assays. Patients were immunized with two doses of vaccine and immunogenicity assessed after each dose using the above tests. CD4+ and CD8+ T cell responses were assessed in a subset using flow‐cytometry. A total of 127 patients were enrolled of which 110 provided serum at all time points. A positive anti‐RBD antibody was seen in 5.0% after one dose and 34.5% after two doses. Neutralizing antibody was present in 26.9%. Of note, 28.5% of patients with anti‐RBD did not have neutralizing antibody. T cell responses in a sub‐cohort of 48 patients showed a positive CD4+ T cell response in 47.9%. Of note, in this sub‐cohort, 46.2% of patients with a negative anti‐RBD, still had a positive CD4+ T cell response. The vaccine was safe and well‐tolerated. In summary, immunogenicity of mRNA‐1273 COVID‐19 vaccine was modest, but a subset of patients still develop neutralizing antibody and CD4+T‐ cell responses. Importantly polyfunctional CD4+T cell responses were observed in a significant portion who were antibody negative, further highlighting the importance of vaccination in this patient population. IRB Statement: This study was approved by the University Health Network Research Ethics Board (CAPCR ID 20–6069).

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…Most studies assessed anti-SARS-CoV-2 immunity through an immunoassay to detect antibodies targeted at the spike protein, including some targeting specifically the receptor-binding domain (RBD) of the spike protein. Thirty studies reported neutralization assay results in addition to anti-SARS-CoV-2 antibody assays [ 34 , 37 , 41 , 48 , 51 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] ]. Thirty-one studies provided data on cellular immunity [ 17 , 21 , 22 , 34 , 37 , 41 , 45 , 46 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 72 , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] , [84] ].…”

“…Forty-seven studies described immunogenicity across various solid organ transplant populations ( n = 5974), mostly in kidney transplant recipients ( n = 3534, 59.2%) ( Table S5 ) [ 18 , [20] , [21] , [22] , [23] , [24] , [25] , [26] , 29 , 34 , 40 , [56] , [57] , [58] ], [ 62 , 63 , 65 , 66 , 69 , 72 , 73 , 75 , 77 , 79 , 81 , 120 , 126 ], [ [136] , [137] , [138] , [139] , [140] , [141] , [142] , [143] , [144] , [145] , [146] , [147] , [148] , [149] , [150] , [151] , [152] , [153] , [154] , [155] , [156] , [157] , [158] , [159] , [160] ]. Twenty-four of those studies included a control group representing overall 1399 participants [ 21 , 34 , 57 , 63 , 66 , 69 , 72 , 73 , 75 , 79 , ...…”

“…Eleven studies reported results of neutralization assays [ 34 , 63 , 66 , 69 , 72 , 77 , 79 , 126 , 145 ]. Non-response rates were close to those in anti-S assays in most studies [ 63 , 72 , 77 , 126 ], while several studies performed the assay only in anti-spike antibody positive participants who mostly tested positive in neutralization assays [ 69 , 79 , 145 ].…”

“…Fourteen studies included data on T-cell immunity, assessed through an ELISpot assay [ [56] , [57] , [58] , 62 , 65 , 75 , 81 ], flow cytometry [ 21 , 34 , 63 , 72 , 79 ] or an IGRA assay [ 21 , 66 ]. Most studies found lower non-response rates in cellular than in antibody response [ [56] , [57] , [58] , 62 , 63 , 72 , 79 , 81 ], while two studies found higher non-response rates in cellular than in antibody response [ 21 , 65 ].…”

Fractionating a COVID-19 Ad5-vectored vaccine improves virus-specific immunity

“…However, there are current attempts to enhance the overall magnitude and durability of immune responses, for example by altering vaccine dosing and boosting regimens. Optimization of prime-boost regimens may obviate the need for "third boosters," which are now recommended for people over 65 years old, as well as patients at high risk of severe illness, including immunosuppressed individuals (8,9). Importantly, the waning of immunity several months post-vaccination is associated with increase in the number of breakthrough infections (10), leading experts to consider additional boosters for the general population.…”