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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
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Neutralization against Omicron variant in transplant recipients after three doses of mRNA vaccine
Deepali Kumar1, Queenie Hu2, Reuben Samson2,3
1University Health Network, Toronto, Ontario, Canada.
Abstract:
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 (log10 ID50 of 2.38 [range 1.34-3.57]). At 3 months, 8/51 (15.7%) were positive (median log10 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.
Insights
Three doses of mRNA COVID-19 vaccines show poor neutralizing antibody responses against the Omicron variant in transplant patients. This highlights a critical gap in protection for this vulnerable population against evolving SARS-CoV-2 strains.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- The Omicron variant is the dominant SARS-CoV-2 strain globally.
- Three mRNA COVID-19 vaccine doses are recommended for transplant recipients.
- Limited data exists on mRNA vaccine immunogenicity against Omicron in this population.
Purpose of the Study:
- To analyze Omicron-specific neutralization in transplant recipients after a three-dose mRNA-1273 vaccine series.
- To assess the durability of neutralizing antibody responses at 1 and 3 months post-vaccination.
Main Methods:
- Utilized a SARS-CoV-2 spike pseudotyped lentivirus assay.
- Compared neutralization against Omicron and Delta variants.
- Analyzed 60 transplant patients (kidney, pancreas, lung, heart, liver).
Main Results:
- Only 18.3% of patients had detectable Omicron neutralization at 1 month (median log10 ID50: 2.38).
- Responses decreased by 3 months (15.7% positive, median log10 ID50: 1.68).
- Omicron neutralization was significantly lower than for wild-type and Delta variants (p < .001).
Conclusions:
- Three mRNA vaccine doses induce inadequate neutralizing responses against the Omicron variant in transplant recipients.
- A significant proportion of patients with anti-RBD responses lacked Omicron-specific neutralization.
- Further strategies are needed to enhance COVID-19 vaccine effectiveness in immunocompromised individuals.
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