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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).

Seeds respond to multiple different environmental stimuli that regulate germination. Nitrate stimulates germination in many plants but how it does so remains unclear. Here we show that the Arabidopsis NIN-like protein 8 (NLP8) is essential for nitrate-promoted seed germination. Seed germination in nlp8 loss-of-function mutants does not respond to nitrate. NLP8 functions even in a nitrate reductase-deficient mutant background, and the requirement for NLP8 is conserved among Arabidopsis accessions. NLP8 reduces abscisic acid levels in a nitrate-dependent manner and directly binds to the promoter of CYP707A2, encoding an abscisic acid catabolic enzyme. Genetic analysis shows that NLP8-mediated promotion of seed germination by nitrate requires CYP707A2. Finally, we show that NLP8 localizes to nuclei and unlike NLP7, does not appear to be activated by nitrate-dependent nuclear retention of NLP7, suggesting that seeds have a unique mechanism for nitrate signalling.

The SARS‐CoV‐2 virus Omicron variant has now supplanted wild‐type virus as the dominant circulating strain globally. Three doses of mRNA COVID‐19 vaccine are recommended for transplant recipients as their primary vaccine series. However, the immunogenicity of mRNA vaccines as they specifically relate to the Omicron variant are not well studied. We analyzed Omicron‐specific neutralization in transplant recipients after three‐doses of mRNA‐1273 vaccine. Neutralization was determined using a SARS‐CoV‐2 spike pseudotyped lentivirus assay with constructs for Omicron and Delta variants. A total of 60 transplant patients (kidney, kidney‐pancreas, lung, heart, liver) were analyzed 1 month and 3 months after completion of three doses of mRNA‐1273. At 1 month, 11/60 (18.3%) patients had detectable neutralizing antibody responses to Omicron (log 10 ID50 of 2.38 [range 1.34–3.57]). At 3 months, 8/51 (15.7%) were positive (median log 10 ID50 [1.68; range 1.12–3.61; approximate fivefold reduction over time]). The proportion of positive patients was lower for Omicron versus wild‐type, and Omicron vs. Delta ( p < .001). No demographic variables were found to be significantly associated with Omicron response. Many patients with a positive anti‐RBD response still had undetectable Omicron‐specific neutralizing antibody. In conclusion, three doses of mRNA vaccine results in poor neutralizing responses against the Omicron variant in transplant patients.

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