While a fourth vaccine dose does increase anti-spike immunoglobin-G (IgG) and neutralising capacity against many COVID-19 variants of concern (VOCs), some solid-organ transplant recipients may remain at a high risk for Omicron infection despite receiving vaccine boosters. This is the concluding message of an observational cohort study published in Transplantation.
In their report, Andrew Karaba (Johns Hopkins University School of Medicine, Baltimore, USA) and colleagues state that, because of this, further protective interventions or alternative vaccination strategies should be “urgently explored”. “Additional strategies, such as modulation of immunosuppressant regimens before additional vaccine doses, vaccines with alternative antigen sequences, or broadly neutralising passive immunity products, such as monoclonal antibody cocktails or high-titer convalescent plasma, may be necessary to provide protection in highly immunosuppressed solid-organ transplant recipients,” they write.
The researchers begin by detailing that humoral responses to COVID-19 vaccines are attenuated in these patients, necessitating additional booster vaccinations, and that the Omicron variant demonstrates “substantial immune evasion”. It is unknown whether additional vaccine doses increase neutralising capacity of plasma against this VOC among solid-organ transplant recipients, they add.
To evaluate this, the researchers enrolled solid-organ transplant recipients in a national (USA), prospective observational study of immunocompromised COVID-19 vaccine recipients, measuring total anti-S antibody, anti-receptor binding domain (anti-RBD) and angiotensin-converting enzyme 2 (ACE2) neutralisation to VOCs.
A total of 25 solid-organ transplant recipients (average age=59 years, 56% female) with low seroresponse were included, and underwent anti-SARS-CoV-2 spike and RBD IgG testing using a commercially available, multiplex enzyme-linked immunosorbent assay (ELISA) test both before and after receiving a fourth COVID-19 vaccine dose. Karaba and colleagues detail that surrogate neutralisation was measured against full-length spike proteins of the vaccine strain, and five VOCs, including Delta and Omicron. Changes in IgG level and percentage ACE2 inhibition (%ACE2i) were compared using the paired Wilcoxon signed-rank test.
Their results are as follows:
- Anti-RBD and anti-spike seropositivity increased post-fourth vaccine dose, from 56% to 84% and 68% to 88%, respectively
- Median anti-spike antibody—as measured by World Health Organization binding antibody units—significantly increased post-fourth vaccine dose, from 42.3 to 228.9
- Median %ACE2i also significantly increased against the vaccine strain (5.8% to 20.6%) and the Delta variant (9.1% to 17.1%)
- However, neutralisation versus Omicron was poor, did not increase post-fourth vaccine dose (4.1% to 0.5%) and was significantly lower than boosted healthy controls
“Although this cohort may not be representative of all vaccinated solid-organ transplant recipients, it does reflect a common and concerning subgroup of persons who seem to be at high risk for SARS-CoV-2 Omicron variant infection despite receiving four vaccine doses,” the researchers write, discussing their findings. “Importantly, at least one participant had evidence of prior infection, which—in combination with three-dose vaccination—connotes potent ‘hybrid immunity’ in the immunocompetent population, yet did not generate Omicron neutralisation.”
The authors acknowledge some limitations of their study, including the fact it was a small, observational convenience sample of people pursuing a fourth COVID-19 vaccine dose in the community and, as such, “may not represent the greater solid-organ transplant recipient population”.
Nevertheless, Karaba and colleagues conclude that these findings suggest that additional and booster dosing of the original vaccines to select solid-organ transplant recipients may not generate robust protection against infection in the form of neutralising antibodies against the Omicron variant, or future variants evolved from Omicron.