mRNA-based COVID-19 vaccination of lung transplant recipients with prior SARS-CoV-2 infection induces durable SARS-CoV-2-specific antibodies and T cells

Sep 3, 2024Vaccine

mRNA COVID-19 vaccines produce lasting virus-specific antibodies and T cells in lung transplant patients who had COVID-19 before

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Abstract

At a median of 184 days after prior SARS-CoV-2 infection, lung transplant recipients were vaccinated twice with the mRNA-1273 COVID-19 vaccine.

Most lung transplant recipients with prior infection had detectable spike-specific antibodies and T cells before vaccination.
Spike-specific antibody levels increased significantly after the first vaccination, with an additional increase after the second vaccination.
Nucleocapsid-specific antibodies decreased during the study period, suggesting no further breakthrough infections occurred.
An increase in T cells producing IFN-γ was observed after the first vaccination, but no further boost was detected after the second vaccination.
Antibody levels and virus-specific T cell responses remained significantly higher than pre-vaccination levels at 6 months post-vaccination.
Neutralizing antibodies were detected against the ancestral strain and showed some cross-reactivity with the Omicron BA.5 variant.

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Lung transplant recipients (LTRs) are particularly at risk of developing severe coronavirus disease-2019 (COVID-19), but are also difficult to protect by vaccination due to their immunocompromised state. Here, we investigated the immunogenicity of mRNA-based COVID-19 vaccines in LTRs who had a prior natural SARS-CoV-2 infection. At a median of 184 days after SARS-CoV-2 infection, LTRs were vaccinated twice with the mRNA-1273 COVID-19 vaccine, with a 28-day interval. Blood samples were obtained pre-vaccination, 28 days after the first dose, and 28 days and 6 months after the second dose. Spike (S-) and nucleocapsid (N-) specific antibodies were measured, as well as neutralization of the ancestral and Omicron BA.5 variant. S-specific T cell responses were evaluated using IFN-γ ELISpot，IGRA, and activation markers by flow cytometry. Phenotyping of T cells was performed by using high-resolution spectral flow cytometry. Most LTRs with prior infection had detectable S-specific antibodies and T cells at baseline. After the first vaccination, S-specific antibody levels increased significantly; an additional increase was observed after the second vaccination. N-specific antibodies decreased during the study period, indicative of the fact that no further breakthrough infections occurred. An increase in IFN-γ producing T cells was observed after the first vaccination, but no additional boost could be detected after the second vaccination. Antibody levels and virus-specific T cell responses remained significantly higher compared to pre-vaccination levels at 6 months post-vaccination, indicating an additive and durable effect of vaccination after infection in LTRs. Neutralizing antibodies were detected against the ancestral strain and retained cross-reactivity with Omicron BA.5, albeit at lower levels. Moreover, the quantity and phenotype of SARS-CoV-2 spike-specific T cells were similar in LTRs compared to controls with hybrid immunity. In conclusion, mRNA-based COVID-19 vaccines are immunogenic in LTRs with prior immunity, and antibody and T cell responses are durable up to 6 months post-vaccination.

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