Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study

Liu, Hong-Hong; Xie, Yunbo; Yang, Bao-Peng; Wen, Huan-Yue; Yang, Peng-Hui; Lu, Jin-E; Liu, Yan; Chen, Xi; Qu, Meng-Meng; Zhang, Yang; Hong, Wei-Guo; Li, Yong-Gang; Fu, Junliang; Wang, Fu-Sheng

doi:10.1038/s41392-024-01846-9

Cited by 3 publications

References 52 publications

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Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Yu,

Wang,

Liu

et al. 2024

Preprint

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Monoclonal antibody (mAb) therapeutics hold promise for both preventing and treating infectious diseases, especially among vulnerable populations. However, the emergence of various variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges for current mAb treatments, emphasizing the need for more potent and broadly neutralizing antibodies. In this study, we employed an unbiased screening approach to discover broadly neutralizing antibodies and successfully isolated two mAbs from individuals with only exposure to ancestral SARS-CoV-2. One of these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum of SARS-CoV-2 variants, including the latest JN.1 and KP.2 variants, with consistent IC50values ranging from ∼1 to 5 ng/mL. Notably, it also displayed broad neutralization activity against SARS-CoV and related sarbecoviruses, such as WIV1, SHC014, RaTG13, and GD-Pangolin. Structural analysis revealed that these mAbs target shared hotspot but mutation-resistant epitopes, with their Fabs locking the RBD in the “down” conformation through interactions with adjacent Fabs and RBDs, and cross-linking Spike trimers into di-trimers to block viral infection. In vivo studies conducted in a JN.1-infected hamster model validated the protective efficacy of CYFN1006-1, emphasizing its therapeutic potential. These findings suggest that, through meticulous approaches, rare antibodies with cross-neutralization activities against SARS-CoV-2 and related sarbecoviruses can be identified from individuals with exclusively ancestral virus exposure.

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Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Yu,

Wang,

Liu

et al. 2024

Preprint

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Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

Alessandra,

Sara,

Claudia

et al. 2024

J Transl Med

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Background A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022. Methods The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender. Result We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VAC no ), whilst 63% had received 2 (VAC 2 ) or 3 doses (VAC 3 ) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC 3 vs. 43% in VAC 2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S ( p = 0.0060), B ( p = 0.0079), CD8 ( p = 0.0043) and Th2 cell counts ( p = 0.0131) were higher in VAC 2 + 3 compared to VAC no . Delta variant was the most representative in VAC 2 ( n = 13/18, 72%), detected in 41% of VAC no , whereas undetected in VAC 3, and anti-RBD-S production was higher in VAC 2 vs. VAC no ( p = 0.0001), alongside neutralization against Delta ( p = 0141), BA1 ( p = 0.0255), BA4/5 ( p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010). Conclusions Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitu...

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Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

Ruggiero,

Caldrer,

Pastori

et al. 2024

Preprint

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Background A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022. Methods The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); B) Lymphocyte B, CD4 and CD8 T-cell phenotype; C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender. Result We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010). Conclusions Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies.

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Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study

Cited by 3 publications

References 52 publications

Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

Immune signature in vaccinated versus non-vaccinated aged people with COVID-19 pneumonia

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