Developing a platform system for gene delivery: amplifying virus-like particles (AVLP) as an influenza vaccine

Abstract

Delivery of a gene of interest to target cells is highly desirable for translational medicine, such as gene therapy, regenerative medicine, vaccine development, and studies of gene function. Parainfluenza virus 5 (PIV5), a paramyxovirus with a negative-sense RNA genome, normally infects cells without causing obvious cytopathic effect, and it can infect many cell types. To exploit these features of PIV5, we established a system generating self-amplifying, virus-like particles (AVLP). Using enhanced green fluorescent protein (EGFP) as a reporter, AVLP encoding EGFP (AVLP–EGFP) successfully delivered and expressed the EGFP gene in primary human cells, including stem cells, airway epithelial cells, monocytes, and T cells. To demonstrate the application of this system for vaccine development, we generated AVLPs to express the HA and M1 antigens from the influenza A virus strain H5N1 (AVLP–H5 and AVLP–M1H5). Immunization of mice with AVLP–H5 and AVLP–M1H5 generated robust antibody and cellular immune responses. Vaccination with a single dose of AVLP–H5 and M1H5 completely protected mice against lethal H5N1 challenge, suggesting that the AVLP-based system is a promising platform for delivery of desirable genes.

Parainfluenza virus 5 is a next‐generation vaccine vector for human infectious pathogens

“…65,66 Additionally, the absence of the PIV5 structural proteins in the AVLP genome prevents the production and spread of infectious progeny from AVLP-infected cells, making the PIV5-AVLP platform as safe as traditional VLPs. 65 Moreover, the production of replicon-containing VLPs has also been simplified from the previous two-step process to a one-step process. 76 In the case of the PIV5-respiratory syncytial virus (RSV) vaccine, for example, the modified PIV5 only deletes the three structural proteins (M, NP, and HN proteins) to make PIV5-AVLP and the AVLP-based vaccine expressing RSV F generates robust antigenspecific immune responses and protects against RSV infection in mice, indicating that PIV5-AVLP-vectored RSV vaccines show promising potentials as effective RSV vaccines.…”

Topical review on nano-vaccinology: Biochemical promises and key challenges

“…However, vaccines have shown to almost counter these areas of concern. Heterosubtypic immune protection in influenza strains (H1N1, H5N1) is a much-needed approach for rapidly mutating viruses [ 31 , 32 ]. A highly significant pathogen of humans, including HBV, HPV, HIV, DENV-E have been prevented using precisely engineered nano vaccines, that have shown to offer up to 95-100% effective immune protection [ 33 ].…”

Bionanotechnology for vaccine design

“…Vaccination with Qβ-α-Gal nanoparticles protected α-Gal–T knockout mice against Leishmania challenge. In other intriguing work, Wei et al[8●] designed self-amplifying VLPs (AVLPs) that can deliver and amplify foreign genes in target cells without producing progeny. They generated AVLPs that express the influenza antigen hemagglutinin (AVLP-H5) as well as those expressing both hemagglutinin and the M1 matrix protein (AVLP-M1H5)[8●].…”

“…In other intriguing work, Wei et al[8●] designed self-amplifying VLPs (AVLPs) that can deliver and amplify foreign genes in target cells without producing progeny. They generated AVLPs that express the influenza antigen hemagglutinin (AVLP-H5) as well as those expressing both hemagglutinin and the M1 matrix protein (AVLP-M1H5)[8●]. Vaccination with a single dose of AVLP-H5 or AVLP-M1H5 completely protected mice against a lethal challenge with an H5N1 influenza virus strain[8●].…”

“…They generated AVLPs that express the influenza antigen hemagglutinin (AVLP-H5) as well as those expressing both hemagglutinin and the M1 matrix protein (AVLP-M1H5)[8●]. Vaccination with a single dose of AVLP-H5 or AVLP-M1H5 completely protected mice against a lethal challenge with an H5N1 influenza virus strain[8●].…”