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Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical characteristics of nanoparticles shaped their tissue dissemination, cellular uptake, and intracellular trafficking, which eventually determined the activation of antiviral humoral and cellular immunity. Specifically, LNP was mainly internalized by myocyte and subsequently circumvented lysosome degradation, giving rise to humoral-biased immune responses. Meanwhile, CNE and Lipo induced cellular-preferred immunity, which was respectively attributed to the better lysosomal escape in dendritic cells and the superior biodistribution in secondary lymphoid organs. Overall, this study may guide the design and clinical use of mRNA vaccines against COVID-19.

SUBMITTER: Shi Y

PROVIDER: S-EPMC9683711 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

Shi Yingying Y Huang Jiaxin J Liu Yu Y Liu Jing J Guo Xuemeng X Li Jianhua J Gong Liming L Zhou Xin X Cheng Guofeng G Qiu Yunqing Y You Jian J Lou Yan Y

Science advances 20221123 47

The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical char ...[more]

PMID: 36417530

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Project description:BackgroundImmunocompromised patients are at increased risk of severe COVID-19 and impaired vaccine response. In this observational prospective study, we evaluated immunogenicity of the BNT162b2 mRNA vaccine in cohorts of primary or secondary immunocompromised patients.MethodsFive clinical groups of immunocompromised patients [primary immunodeficiency (PID) (n=57), people living with HIV (PLWH) (n=27), secondary immunocompromised patients with a broad variety of underlying rheumatologic (n=23) and homogeneous (multiple sclerosis) neurologic (n=53) conditions and chronic kidney disease (CKD) (n=39)] as well as a healthy control group (n=54) were included. Systemic humoral and cellular immune responses were evaluated by determination of anti-SARS-CoV-2 Spike antibodies using a TrimericS IgG assay (Diasorin) and through quantification of interferon gamma release in response to SARS-CoV-2 antigen with QuantiFERON SARS-CoV-2 assay (Qiagen), respectively. Responses were measured at pre-defined time-points after complete vaccination.ResultsAll healthy controls, PLWH and CKD-patients had detectable antibodies 10 to 14 days (T2) and 3 months (T3) after administration of the second vaccination. In contrast, only 94.5% of the PID, 50.0% of the rheumatologic and 48.0% of neurologic patients developed antibodies at T2 and only 89.1% of the PID, 52.4% of the rheumatologic and 50.0% of neurologic patients developed antibodies at T3. At T3 no significant differences in cellular response between the healthy control group and the PLWH and CKD groups were found, while proportions of reactive subjects were lower in PID and rheumatologic patients and higher in neurologic patients. Humoral and cellular immune responses significantly correlated in the healthy control, PID, PLWH groups for all 3 antigens.ConclusionPatients with acquired or inherited immune disorders may show variable immune responses to vaccination with the BNT162b2 mRNA vaccine against SARS-CoV-2. Whether humoral, cellular or both immune responses are delayed depends on the patient group, therapy and individual risk factors. These data may guide the counselling of patients with immune disorders regarding vaccination of SARS-CoV-2.

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Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

Publications

Structural and biochemical characteristics of mRNA nanoparticles determine anti-SARS-CoV-2 humoral and cellular immune responses.

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