A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Area of Science:

• Vaccinology
• Nanotechnology
• Virology

Background:

• Rotavirus infection causes severe gastroenteritis in children globally, leading to an estimated 200,000 deaths annually, particularly in low-income regions.
• Current rotavirus vaccines require improvement to address the persistent global burden of rotavirus-related diarrhea.

Purpose of the Study:

• To develop and evaluate a novel trivalent nanoparticle-based vaccine targeting the major neutralizing antigens of globally prevalent rotavirus P types.
• To assess the immunogenicity and neutralizing capacity of the P24-VP8* trivalent nanoparticle vaccine candidate.

Main Methods:

• Production of tag-free P24-VP8* nanoparticles presenting VP8* domains from P[8], P[4], and P[6] rotavirus strains using chemical precipitation and ion exchange purification.
• Characterization of nanoparticle self-assembly and VP8*-glycan binding function.
• Evaluation of the trivalent vaccine's immunogenicity (IgG titers) and in vitro neutralization of rotavirus P types in a mouse model.

Main Results:

• Successfully produced tag-free P24-VP8* nanoparticles with preserved VP8*-glycan receptor binding function.
• Intramuscular immunization with the trivalent vaccine induced high IgG titers specific to the three targeted VP8* types in mice.
• Mouse sera demonstrated potent neutralization of all three rotavirus P types in cell culture.

Conclusions:

• The developed P24-VP8* trivalent nanoparticle vaccine is a promising candidate for parenteral administration.
• This vaccine strategy offers a potential new approach to combatting multiple predominant rotavirus P types and reducing rotavirus-related mortality.