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

• Main Authors: Ming Xia, Pengwei Huang, Xi Jiang, Ming Tan
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Viruses
• Subjects: rotavirus; P₂₄-VP8* nanoparticle; rotavirus vaccine; rotavirus VP8*; non-replicating rotavirus vaccine; norovirus P domain
• Online Access: https://www.mdpi.com/1999-4915/13/1/72

Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P₂₄-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P₂₄-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P₂₄-VP8* nanoparticles presenting the VP8*s of P[8], P[⁴], and P[⁶] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P₂₄-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P₂₄-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.