Towards a coronavirus-based HIV multigene vaccine

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Human immunodeficiency virus (HIV) infection is a major global health threat, with costly treatments unaffordable in developing nations.
• There is a critical need for effective vaccination strategies to prevent HIV spread.
• Human coronavirus 229E (HCoV 229E) possesses unique biological features suitable for vaccine vector development.

Purpose of the Study:

• To explore the potential of HCoV 229E-based vectors as a novel vaccine platform for HIV prevention.
• To investigate the mechanisms by which HCoV 229E vectors can target antigen-presenting cells and elicit an immune response.

Main Methods:

• Utilizing the HCoV 229E receptor, human aminopeptidase N (hAPN/CD13), for targeted transduction of dendritic cells (DCs) and macrophages.
• Engineering HCoV 229E-based virus-like particles (VLPs) to replace structural genes with antigen-encoding units.
• Assessing the ability of HCoV 229E VLPs to transduce human DCs and mediate heterologous gene expression.

Main Results:

• HCoV 229E vectors can target professional antigen-presenting cells (APCs) via receptor-mediated endocytosis.
• Structural genes of HCoV 229E can be substituted to create VLPs expressing multiple antigens.
• These engineered VLPs effectively transduce human DCs and facilitate heterologous gene expression within these cells.

Conclusions:

• HCoV 229E-based vectors represent a promising new class of highly efficient vaccine candidates.
• The natural tropism of HCoV 229E for mucosal surfaces and APCs supports its use as a vaccine vector.
• Pre-existing immunity to HCoV 229E is unlikely to impede the efficacy of HCoV 229E-based vaccine vectors in humans.