DNA vaccines for targeting bacterial infections

Abstract

DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles.Keywords bacterial vaccine; cellular and humoral immune responses; DNA vaccine; molecular adjuvants Times have changed since Edward Jenner immunized James Phipps against smallpox in 1796 and created what years later became known as a vaccine [1]. From the first live-attenuated or killed vaccines to the era of DNA vaccines in the early 1990s, molecular biology and microbiology have aided medical research in the development of vaccines against infectious diseases, cancer, allergies and autoimmune diseases by inducing rapid and robust immune responses or by creating immune tolerance [2]. From the time of Jenner's first vaccine until the present day, there have been over 60 licensed vaccines in the USA. These vaccines come in many forms: killed microorganisms, live-attenuated microorganisms, subunits, conjugate vaccines or toxoids. Although there are no US FDA-approved DNA vaccines for use in humans, they are the newest vaccine platform currently in development and have already had success in veterinary medicine [3][4][5][6][7][8].© 2010 Expert Reviews Ltd † Author for correspondence: Tel.: +1 215 349 8591, Fax: +1 215 573 9436, dbweiner@mail.med.upenn.edu. Financial & competing interests disclosureThe authors declare possible commercial conflicts, which may include advising, consulting and collaboration, with Wyeth, Inovio, BMS, Virxsys, Ichor, Merck, Althea, Johnson & Johnson and Aldeveron. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NIH Public Access Author ManuscriptExpert Rev Vaccines. Author manuscript; available in PMC 2011 May 1. Published in final edited form as:Expert Rev Vaccines. 2010 July ; 9(7): 747-763. doi:10.1586/erv.10.57. NIH-PA Author ManuscriptNIH-PA Author Manuscript N...

Evaluation of the immunogenicity and the protective efficacy in mice of a DNA vaccine encoding SP41 from Brucella melitensis

“…injection is the most common route of DNA administration. It seems that dendritic cells, professional antigen-presenting cells, play a major role in the initiation of an immune response in DNA vaccination by efficiently priming T cells with exogenous or endogenous antigens [14].…”

“…DNA vaccination might provide several important advantages over current vaccines, as follows: (i) DNA vaccines mimic the effects of live attenuated vaccines in their ability to induce major histocompatibility complex (MHC) class I restricted CD8+ T-cell responses, which may be advantageous compared with conventional protein-based vaccines, while mitigating some of the safety concerns associated with live vaccines; (ii) DNA vaccines can be manufactured in a relatively cost-effective manner and stored with relative ease [12,13]; (iii) DNA vaccine provides prolonged antigen expression, leading to the amplification of immune response and induces memory responses against infectious agents [14]. This type of vaccine is capable of eliciting the strong CMI that is required for the control of infection by many intracellular agents [15].…”

Peyer’s Patches as a Portal for DNA Delivery by <i>Lactococcus lactis</i> <i>in Vivo</i>

“…1) Despite numerous studies, no DNA vaccines have been licensed for human use to date. The administration of naked DNA is less immunogenic in large animals and humans, probably due to the low level of protein expression.…”

Neisseria gonorrhoeae NspA Induces Specific Bactericidal and Opsonic Antibodies in Mice

“…DNA vaccine consists of a DNA plasmid containing a gene of interest from a pathogen that is able to express the corresponding target antigen in eukaryotic cells under the control of a suitable promoter (19). DNA vaccines are versatile, safe, and simple.…”

“…They can be developed rapidly and inexpensively for the prevention of infections by a wider range of pathogens. Therefore, DNA vaccines are potentially powerful in the prevention of infectious diseases (1,19). To enhance the immune responses, several new strategies have been developed (1).…”