hPIV2 Vector Technology

Creative Biolabs has developed a novel vaccine carrier technology using non-transmissible or single round-infectious human parainfluenza virus type 2 (hPIV2) vector. It is an inactivated paramyxovirus vector carrying a range of vaccine antigens which elicits strong and long-lasting humoral and cellular immune response without adjuvants. hPIV2 has been demonstrated its potential for use in human gene therapy or recombinant vaccine development. Several stable packaging cell lines constitutively expressing fusion (F) protein of hPIV2 have been established by Creative Biolabs for production of the F-defective and single round-infectious hPIV2 vector.

Human Parainfluenza Virus Type 2 (hPIV2)

Human parainfluenza virus type 2 (hPIV2) belongs to the Paramyxovirdae family and is a respiratory pathogen that causes croup and other upper and lower respiratory tract diseases in young children. It has a non-segmented negative-strand RNA genome which encodes seven structural proteins, NP, P/V, M, F, HN, and L. hPIV2 has two surface glycoproteins, the hemagglutininneuraminidase (HN) and fusion (F) protein. Of the viral envelope proteins, the F protein has fusion activity and it reciprocally works with the HN protein to achieve viral envelope-to-cell or cell-to-cell fusion.

hPIV2 attaches to the cell surface receptors via the HN protein, and F protein triggers the envelope-cell fusion. F protein-mediated fusion allows the viral nucleocapsid to enter a host cell. F protein also induces membrane fusion between host cells (syncytial formation). Transduction of the F-defective replicon RNA into cells led to the release of the infectious particles that packaged the replicon RNA (named as hPIV2ΔF) without detectable mutations, limiting the infectivity to a single round.

Fig.1 Structure of Human parainfluenza virus type 2. (Moscona, A., 2005)

The Advantages of hPIV2 Vector Technology

Non-transmissible or a single round-infectious replicon form of the hPIV2 vector is desirable for clinical safety as biopharmaceuticals. Transduction of the replicon RNA lacking an F gene (hPIV2ΔF) into the target cell line expressing F protein led to the release of single round-infectious particles that packaged the replicon RNA with high production efficiency. Creative Biolabs has developed a reverse genetics system for the production of infectious hPIV2 lacking the F gene (hPIV2ΔF), wherein various advantages for vaccine therapy exist, including:

• Safety. The lack of either an F or HN envelope gene not only abolishes the progeny generation but also prevents deleterious fusion events to neighboring cells.
• Available versatile and long antigens.
• Cytoplasmic replication/transcription.
• Non-transmissible infectivity.
• Extremely high transduction efficacy in various types of target cells.
• Eliciting strong and long-lasting humoral and cellular immune response without adjuvants.
• Simple and efficient manufacturing process.
• Cost effective.

Preparation of hPIV2 Vector Vaccines

• Constructing recombinant hPIV2 carrying a range of vaccine antigens on the surface
• Fully inactivating the RNA genome of recombinant hPIV2 to non-replication
• The protein structure of the envelope proteins still maintains immunogenicity and receptor-mediated fusion ability like live recombinant hPIV2.

Applications of hPIV2 Vector Technology

• Universal flu vaccine
• Respiratory syncytial virus (RSV) vaccine
• Ebola virus vaccine
• Tuberculosis (TB) vaccine
• Cancer vaccine

hPIV2 is a useful tool for vaccine development as a novel type of paramyxoviral vector, which is a single-round infectious vector and has potential adjuvant activity. Creative Biolabs specializes in creating novel vaccine technology platforms to promote the prevention and treatment of infectious diseases and cancer. We strive with competence and confidence to meet your demand for creating novel conjugates and to promote vaccine development.

Reference

1. Moscona, A., (2005). "Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease." Journal of Clinical Investigation, 115(7), 1688-98.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.