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Cross-reactivity00:42

Cross-reactivity

Overview
Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...

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RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques.

Hélène Letscher1, Delphine Guilligay2, Gregory Effantin2

  • 1Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT/UMR-S 1184), Fontenay-aux-Roses & Le Kremlin-Bicêtre, Paris, France. helene.letscher@cea.fr.

NPJ Vaccines
|March 30, 2025
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Developing a novel SARS-CoV-2 SΔRBD vaccine candidate, researchers found it provides improved protection against lung infection compared to standard mRNA vaccines. This new approach enhances antibody-based immunity against evolving variants.

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Area of Science:

  • Immunology
  • Virology
  • Vaccine Development

Background:

  • SARS-CoV-2 variants with mutations in the receptor binding domain (RBD) pose challenges to vaccine efficacy.
  • The RBD is a key target for immune responses, but its rapid evolution necessitates alternative strategies.
  • Steering immune responses towards more conserved regions of the spike (S) glycoprotein is crucial for broad protection.

Purpose of the Study:

  • To generate and characterize SARS-CoV-2 S glycoprotein trimers lacking the RBD (SΔRBD).
  • To evaluate the immunogenicity and protective efficacy of SΔRBD-based virus-like particles (SΔRBD-LV) in a heterologous prime-boost vaccination strategy.
  • To compare the efficacy of SΔRBD-LV against SARS-CoV-2 variants, including Omicron XBB.3, relative to a standard mRNA vaccine.

Main Methods:

  • Generation of SΔRBD trimers stabilized by formaldehyde cross-linking.
  • Cryo-electron microscopy (cryo-EM) to determine the structure of SΔRBD.
  • Production of synthetic virus-like particles (SΔRBD-LV) by coating SΔRBD onto lipid vesicles.
  • Heterologous prime-boost immunization in cynomolgus macaques using Comirnaty mRNA vaccine and SΔRBD-LV.
  • Assessment of antibody titers, neutralization capacity against SARS-CoV-2 variants, and protection upon Omicron XBB.3 challenge.

Main Results:

  • Cryo-EM confirmed SΔRBD maintains the native prefusion conformation, stabilized by a cross-link.
  • SΔRBD-LV boost in macaques induced comparable antibody titers and neutralization of various SARS-CoV-2 variants, including Omicron, to a third Comirnaty dose.
  • Both vaccination strategies offered similar overall protection against infection after Omicron XBB.3 challenge.
  • The SΔRBD-LV boost demonstrated superior protection against lung infection compared to the Comirnaty-only strategy.

Conclusions:

  • SΔRBD is highly immunogenic and elicits potent antibody responses.
  • A heterologous prime-boost strategy with SΔRBD-LV offers improved protection against lung infection, suggesting superior antibody-based immunity.
  • SΔRBD-based vaccines represent a promising approach to enhance protection against evolving SARS-CoV-2 variants.