Bacteriophage-mediated nucleic acid immunisation

Abstract

Whole bacteriophage lambda particles, containing reporter genes under the control of the cytomegalovirus promoter (P(CMV)), have been used as delivery vehicles for nucleic acid immunisation. Following intramuscular injection of mice with lambda-gt11 containing the gene for hepatitis B surface antigen (HBsAg), anti-HBsAg responses in excess of 150 mIU ml(-1) were detected. When isolated peritoneal macrophages were incubated with whole lambda particles containing the gene for green fluorescent protein (GFP) under the control of P(CMV), GFP antigen was detected on the macrophage surface 8 h later. Results suggested that direct targeting of antigen-presenting cells by bacteriophage 'vaccines' may occur, leading to enhanced immune responses compared to naked DNA delivery. Bacteriophage DNA vaccines offer several advantages: they do not contain antibiotic resistance genes, they offer a large cloning capacity (approximately 15 kb), the DNA is protected from environmental degradation, they offer the potential for oral delivery, and large-scale production is cheap, easy and extremely rapid.

Phage Library Screening for the Rapid Identification and In Vivo Testing of Candidate Genes for a DNA Vaccine against Mycoplasma mycoides subsp. mycoides Small Colony Biotype

“…After challenge, mice vaccinated with clone -A8 also exhibited a reduced level of mycoplasmemia compared to controls, suggesting that the MSC_0397 lipoprotein has a protective effect in the mouse model when delivered as a bacteriophage DNA vaccine. Bacteriophage-mediated immunoscreening using an appropriate vector system offers a rapid and simple technique for the identification and immediate testing of putative candidate vaccines from a variety of pathogens.Whole bacteriophage (phage) particles have recently been described as highly efficient DNA vaccine delivery vehicles (6,7,17,20), inducing significant antibody responses in both laboratory mice (7) and larger animals such as rabbits (20) and sheep (33). Bacteriophages are viruses of bacteria and are metabolically inert, requiring the host bacterium for growth and propagation.…”

“…Whole bacteriophage (phage) particles have recently been described as highly efficient DNA vaccine delivery vehicles (6,7,17,20), inducing significant antibody responses in both laboratory mice (7) and larger animals such as rabbits (20) and sheep (33). Bacteriophages are viruses of bacteria and are metabolically inert, requiring the host bacterium for growth and propagation.…”

Therapeutic and Prophylactic Applications of Bacteriophage Components in Modern Medicine

“…2) (Clark and March 2006). Several l-based DNA vaccines for infectious diseases have been prepared that have shown promising results in animal models (Clark and March 2004b;March et al 2004). …”

Immunocompatibility of Bacteriophages as Nanomedicines

“…Modified phage particles package their nucleic acid carrying the vaccine expressing sequence in their protein coat, likely protecting it from sources of degradation, before and after administration. Different small and large animal models have been vaccinated by phage DNA vaccines, and the results demonstrated a significantly higher and long-lasting antibody response compared to naked DNA vaccine or even purified recombinant protein [23][24][25]. Furthermore, as an exogenous antigen, the phage particle efficiently targets antigen-presenting cells (APCs), thereby stimulating a superior specific humoral immune response to the vaccine [4], compared to standard "naked" DNA vaccine approaches.…”