Fusion protein of rotavirus VP6 and SARS-CoV-2 receptor binding domain induces T cell responses

Kirsi Tamminen, Suvi Heinimäki, Stina Gröhn, Vesna Blazevic

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Abstract

Vaccines based on mRNA and viral vectors are currently used in the frontline to combat the ongoing pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, there is still an urgent need for alternative vaccine technologies inducing/boosting long-lasting and cross-reactive immunity in different populations. As a possible vaccine candidate, we employed the rotavirus VP6-protein platform to construct a fusion protein (FP) displaying receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) at the N-terminus of VP6. The recombinant baculovirus-insect cell produced VP6-RBD FP was proven antigenic in vitro and bound to the human angiotensin-converting enzyme 2 (hACE2) receptor. The FP was used to immunize BALB/c mice, and humoral-and T cell-mediated immune responses were investigated. SARS-CoV-2 RBD-specific T cells were induced at a high quantity; however, no RBD or S-specific antibodies were detected. The results suggest that conformational B cell epitopes might be buried inside the VP6, while RBD-specific T cell epitopes are available for T cell recognition after the processing and presentation of FP by the antigen-presenting cells. Further immunogenicity studies are needed to confirm these findings and to assess whether, under different experimental conditions, the VP6 platform may present SARS-CoV-2 antigens to B cells as well.

Original languageEnglish
Article number733
JournalVaccines
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2021
Publication typeA1 Journal article-refereed

Keywords

  • Antibodies
  • COVID-19
  • Delivery platform
  • Immune response
  • SARS-CoV-2
  • T cells
  • Vaccines
  • VP6

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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