Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines

Sun, Cong; Yuan, Runyu; Xie, Chu; Sun, Jiufeng; Fang, Xin-Yan; Hu, Yisha; Yu, Xiaohui; Liu, Zheng; Zeng, Mu‐Sheng; Kang, Yinfeng

doi:10.1128/jvi.00383-22

Cited by 3 publications

(2 citation statements)

References 74 publications

(70 reference statements)

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“…Consequently, studies have shown that antibodies from previously infected or vaccinated individuals have reduced binding and decreased neutralization against the B.1.1.7 (53, 64), B.1.351 (53, 64), B.1.617.2 (65–67), and B.1.1.529 variants (68, 69). To address the reduced neutralization activity against circulating strains, there are ongoing efforts to update vaccines as the virus mutates by either immunizing with a contemporary SARS-CoV-2 variant (70) or multivalent vaccines (71, 72), or by developing vaccination strategies to elicit higher titers of cross-reactive antibodies by immunizing with only the S1 (73), S2 (74), RBD (75), or a mixture of immunogenic SARS-CoV-2 peptides (76).…”

Section: Introductionmentioning

confidence: 99%

Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso–RBD Antibodies

Curtis,

Shin,

Hederman

et al. 2023

Preprint

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While our understanding of SARS-CoV-2 pathogenesis and antibody responses following infection and vaccination has improved tremendously since the outbreak in 2019, the sequence identities and relative abundances of the individual constituent antibody molecules in circulation remain understudied. Using Ig-Seq, we proteomically profiled the serological repertoire specific to the whole ectodomain of SARS-CoV-2 prefusion-stabilized spike (S) as well as to the receptor binding domain (RBD) over a 6-month period in four subjects following SARS-CoV-2 infection before SARS-CoV-2 vaccines were available. In each individual, we identified between 59 and 167 unique IgG clonotypes in serum. To our surprise, we discovered that ∼50% of serum IgG specific for RBD did not recognize prefusion-stabilized S (referred to as iso–RBD antibodies), suggesting that a significant fraction of serum IgG targets epitopes on RBD inaccessible on the prefusion-stabilized conformation of S. On the other hand, the abundance of iso–RBD antibodies in nine individuals who received mRNA-based COVID-19 vaccines encoding prefusion-stabilized S was significantly lower (∼8%). We expressed a panel of 12 monoclonal antibodies (mAbs) that were abundantly present in serum from two SARS-CoV-2 infected individuals, and their binding specificities to prefusion-stabilized S and RBD were all in agreement with the binding specificities assigned based on the proteomics data, including 1 iso–RBD mAb which bound to RBD but not to prefusion-stabilized S. 2 of 12 mAbs demonstrated neutralizing activity, while other mAbs were non-neutralizing. 11 of 12 mAbs also bound to S (B.1.351), but only 1 maintained binding to S (B.1.1.529). This particular mAb binding to S (B.1.1.529) 1) represented an antibody lineage that comprised 43% of the individual’s total S-reactive serum IgG binding titer 6 months post-infection, 2) bound to the S from a related human coronavirus, HKU1, and 3) had a high somatic hypermutation level (10.9%), suggesting that this antibody lineage likely had been elicited previously by pre-pandemic coronavirus and was re-activated following the SARS-CoV-2 infection. All 12 mAbs demonstrated their ability to engage in Fc-mediated effector function activities. Collectively, our study provides a quantitative overview of the serological repertoire following SARS-CoV-2 infection and the significant contribution of iso–RBD antibodies, demonstrating how vaccination strategies involving prefusion-stabilized S may have reduced the elicitation of iso–RBD serum antibodies which are unlikely to contribute to protection.

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Section: Introductionmentioning

confidence: 99%

Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso–RBD Antibodies

Curtis,

Shin,

Hederman

et al. 2023

Preprint

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show abstract

“…Nevertheless, our data show that vaccination with 3 doses has an impact on disease duration, that might be due also to an increased mucosal IgA and/or IgG content in a subgroup of responders and not only to cellular response ( 56 ). In this way, development of new vaccines able to induce a stronger IgA response might hopefully strengthen the protection ( 57 ). However, due to the emergence of VOCs and the evidence of a reduced neutralizing efficacy of mabs as well as natural antibodies ( 58 ) therapeutic strategies based on the use of antivirals might be impaired to a lesser extent by SARS-CoV-2 “escape mechanisms”.…”

Section: Discussionmentioning

confidence: 99%

Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic

et al. 2022

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BackgroundSince the beginning of the COVID-19 pandemic, patients with Inborn Errors of Immunity have been infected by SARS-CoV-2 virus showing a spectrum of disease ranging from asymptomatic to severe COVID-19. A fair number of patients did not respond adequately to SARS-CoV-2 vaccinations, thus early therapeutic or prophylactic measures were needed to prevent severe or fatal course or COVID-19 and to reduce the burden of hospitalizations.MethodsLongitudinal, multicentric study on patients with Inborn Errors of Immunity immunized with mRNA vaccines treated with monoclonal antibodies and/or antiviral agents at the first infection and at reinfection by SARS-CoV-2. Analyses of efficacy were performed according to the different circulating SARS-CoV-2 strains.ResultsThe analysis of the cohort of 192 SARS-CoV-2 infected patients, across 26 months, showed the efficacy of antivirals on the risk of hospitalization, while mabs offered a positive effect on hospitalization, and COVID-19 severity. This protection was consistent across the alpha, delta and early omicron waves, although the emergence of BA.2 reduced the effect of available mabs. Hospitalized patients treated with mabs and antivirals had a lower risk of ICU admission. We reported 16 re-infections with a length of SARS-CoV-2 positivity at second infection shorter among patients treated with mabs. Treatment with antivirals and mabs was safe.ConclusionsThe widespread use of specific therapy, vaccination and better access to care might have contributed to mitigate risk of mortality, hospital admission, and severe disease. However, the rapid spread of new viral strains underlines that mabs and antiviral beneficial effects should be re- evaluated over time.

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Self‐Assembled Multiepitope Nanovaccine Provides Long‐Lasting Cross‐Protection against Influenza Virus

Nie,

Wang,

et al. 2023

Adv Healthcare Materials

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Seasonal influenza vaccines typically provide strain‐specific protection and are reformulated annually, which is a complex and time‐consuming process. Multiepitope vaccines, combining multiple conserved antigenic epitopes from a pathogen, can trigger more robust, diverse, and effective immune responses, providing a potential solution. However, their practical application is hindered by low immunogenicity and short‐term effectiveness. In this study, multiple linear epitopes from the conserved stem domain of hemagglutinin and the ectodomain of matrix protein 2 are combined with the Helicobacter pylori ferritin, a stable self‐assembled nanoplatform, to develop an influenza multiepitope nanovaccine, named MHF. MHF is prokaryotically expressed in a soluble form and self‐assembles into uniform nanoparticles. The subcutaneous immunization of mice with adjuvanted MHF induces cross‐reactive neutralizing antibodies, antibody‐dependent cell‐mediated cytotoxicity, and cellular immunity, offering complete protection against H3N2 as well as partial protection against H1N1. Importantly, the vaccine cargo delivered by ferritin triggers epitope‐specific memory B‐cell responses, with antibody level persisting for over 6 months post‐immunization. These findings indicate that self‐assembled multiepitope nanovaccines elicit potent and long‐lasting immune responses while significantly reducing the risk of vaccine escape mutants, and offer greater practicality in terms of scalable manufacturing and genetic manipulability, presenting a promising and effective strategy for future vaccine development.

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Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines

Cited by 3 publications

References 74 publications

Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso–RBD Antibodies

Characterization of SARS-CoV-2 Convalescent Patients’ Serological Repertoire Reveals High Prevalence of Iso–RBD Antibodies

Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic

Self‐Assembled Multiepitope Nanovaccine Provides Long‐Lasting Cross‐Protection against Influenza Virus

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