Immunocontraception: Filamentous Bacteriophage as a Platform for Vaccine Development

Abstract

Background: Population control of domestic, wild, invasive, and captive animal species is a global issue of importance to public health, animal welfare and the economy. There is pressing need for effective, safe, and inexpensive contraceptive technologies to ad-dress this problem. Contraceptive vaccines, designed to stimulate the immune system in order to block critical reproductive events and suppress fertility, may provide a solution. Fil-amentous bacteriophages can be used as platforms for development of such vaccines.Objective: In this review authors highlight structural and immunogenic properties of fila-mentous phages, and discuss applications of phage-peptide vaccines for advancement of immunocontraception technology in animals.Results: Phages can be engineered to display fusion (non-phage) peptides as coat proteins. Such modifications can be accomplished via genetic manipulation of phage DNA, or by chemical conjugation of synthetic peptides to phage surface proteins. Phage fusions with antigenic determinants induce humoral as well as cell-mediated immune responses in ani-mals, making them attractive as vaccines. Additional advantages of the phage platform include environmental stability, low cost, and safety for immunized animals and those ad-ministering the vaccines.Conclusion: Filamentous phages are viable platforms for vaccine development that can be engineered with molecular and organismal specificity. Phage-based vaccines can be pro-duced in abundance at low cost, are environmentally stable, and are immunogenic when administered via multiple routes. These features are essential for a contraceptive vaccine to be operationally practical in animal applications. Adaptability of the phage platform also makes it attractive for design of human immunocontraceptive agents.

Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases

“…Generally, short peptides ~8 amino acid residues containing B-cell or T-cell epitopes are optimal for display [30]. However, larger peptides, domains, or even large full-length antigens could be displayed, but the copy number will be quite low as these need to be assembled along with the WT capsid protein that forms the bulk of the capsid structure [157]. Both the pIII and pVIII capsid proteins could be used for display, however the very low copy number of pIII makes it less desirable for the purposes of vaccine delivery.…”

The development of inovirus-associated vector vaccines using phage-display technologies

“…They are capable of stimulating humoral and cellular immune responses and do not pose known health risks to animals or humans. IAVs can be administered safely in high doses through multiple routes, enhancing their usage in a variety of contexts [107]. With their cost-efficient production, structural simplicity, and record of success in a variety of contexts, IAVs have the potential to be exploited for many new vaccines in humans and animals against a variety of diseases.…”

Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats

“…[13][14][15] In addition to these characteristics, low cost and phage stability in various environmental conditions make phages an attractive antigen delivery system for vaccine development, including vaccines for suppression of fertility. 16,17 Recently, we have developed several phage-based vaccines against GnRH that were tested in male mice and demonstrated promising contraceptive properties. 12 These proof of principle results in mice warranted the next logical step in evaluating the vaccines in the target species, cats.…”

“…13–15 In addition to these characteristics, low cost and phage stability in various environmental conditions make phages an attractive antigen delivery system for vaccine development, including vaccines for suppression of fertility. 16,17…”