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Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

ABSTRACT: Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.

SUBMITTER: Park HS

PROVIDER: S-EPMC8983140 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Park Han-Sol HS Shapiro Janna R JR Sitaras Ioannis I Woldemeskel Bezawit A BA Garliss Caroline C CC Dziedzic Amanda A Sachithanandham Jaiprasath J Jedlicka Anne E AE Caputo Christopher A CA Rousseau Kimberly E KE Thakar Manjusha M Suwanmanee San S Hauk Pricila P Aliyu Lateef L Majewska Natalia I NI Koley Sushmita S Patel Bela B Broderick Patrick P Mosnaim Giselle G Heath Sonya L SL Spivak Emily S ES Shenoy Aarthi A Bloch Evan M EM Gniadek Thomas J TJ Shoham Shmuel S Casadevall Arturo A Hanley Daniel D Cox Andrea L AL Laeyendecker Oliver O Betenbaugh Michael J MJ Cramer Steven M SM Mostafa Heba H HH Pekosz Andrew A Blankson Joel N JN Klein Sabra L SL Tobian Aaron Ar AA Sullivan David D Gebo Kelly A KA

JCI insight 20220308 5

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infecti ...[more]

PMID: 35104245

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Project description:Vaccination against SARS-CoV-2 has been successful in protecting patients with cancer from severe infections, but how immune responses against COVID-19 vaccination interact with those elicited during cancer immunotherapy has not been fully described. Immune checkpoint blockade (ICB) disrupts inhibitory pathways in immune cells to improve function and induce tumor immunity but can often cause serious immune related adverse events (IRAEs). Because COVID-19 vaccination and ICB both boost immune responses, it is imperative to understand if combining these regimens causes synergistic enhancement of the immune system. Specifically, whether ICB impacts anti-vaccine immunity in previously vaccinated patients is important since a large percentage of newly diagnosed cancer patients eligible for immunotherapy will have already been vaccinated against COVID-19. To address this, we investigated the influence of ICB on SARS-CoV-2-spike protein (SP) antibody titers and T cell responses in cancer patients previously vaccinated against COVID-19. Human blood samples were collected from 29 vaccinated patients and 12 unvaccinated control patients at baseline (prior to ICB) and following two rounds of ICB infusion. Anti-SARS-CoV-2-SP IgG titers and T cell responses were quantified. Compared to responses at baseline, there was no significant difference in these immune responses after immunotherapy in vaccinated individuals (P=0.4583, P=0.4571, respectively). We interpret these results as evidence that ICB immunotherapy does not significantly enhance SARS-CoV-2-specific antibody titers or T cell responses. Although our study lacks corresponding IRAE rates, the results provide humoral and cellular immunological data that support recent reports documenting the clinical safety and efficacy of COVID-19 vaccination in patients receiving ICB. Additional longitudinal prospective studies, such as the VOICE study (ClinicalTrials.gov identifier NCT04715438) and CAPTURE study (ClinicalTrials.gov identifier NCT03226886), are warranted and will provide broader safety and immunological data defining the effect of systemic cancer therapies on COVID-19 immunity.

Dataset Information

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Publications

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

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