The development of ghost vaccines trials

ABSTRACT

Introduction

Bacterial ghosts are intact bacterial cell envelopes that are emptied of their content by gentle biological or chemical poring methods. Ghost techniques increase the safety of the killed vaccines, while maintaining their antigenicity due to mild preparation procedures. Moreover, ghost-platforms may express and/or carry several antigens or plasmid-DNA encoding for protein epitopes.

Areas covered

In this review, the development in ghost-vaccine production over the last 30 years is classified and discussed. The different applications of ghost-vaccines, how they trigger the immune system, their advantages and limitations are displayed. The phage-mediated lysis, molecular manipulation of the lysis-genes, and the biotechnological production of ghosts are described. The trials are classified according to the pattern of lysis and to the type of bacteria. Further subdivision includes chronological ordered application of the ghost as alternative-killed vaccine, recombinant antigen platform, plasmid DNA carrier, adjuvants, and dendritic cell inducer. Particular trials for specific pathogens or from distinct research schools are gathered.

Expert opinion

Ghosts are highly qualified to act as immune-presenting platforms that express and/or carry several recombinant and DNA vaccines, as well as, being efficient alternative-killed vaccines. The coming years will show more molecular advances to develop ghost-production and to express more antigens.

KEYWORDS:

• Ghosts
• vaccines
• immunotherapy
• vaccine platform
• e-mediated lysis

Article highlights

• Ghosts are intact microbial cells, most commonly Gram-negative bacteria voided by gentle chemical or biological poring methods. They represent a development for the whole-cell killed vaccines. E. coli, Salmonella spp. and Vibrio cholerae are the most frequently applied bacteria for ghost production.

• Ghost-vaccine techniques enable the production of safer alternative-killed vaccines, platforms that express a wide number of antigens and DNA encoding epitopes, carrier-envelopes for DNA vaccines and antigens, adjuvants, and dendritic cell enhancers.

• The ghost production techniques developed in the 1990s depending on the E-lysis gene operated by several thermal and chemical expression regulators. In 2013, the sponge-like chemical protocols evolved to produce ghosts from Candida and Gram-positive together with Gram-negative bacteria.

• In an attempt to enhance the productivity of ghost, several mutations and developments in the E-lysis expression cassette were applied. For enhancing the safety, genes encoding for the holin-endolysin system, for nucleases and for antibacterial peptides were incorporated into the E-lysis cassettes. Lately, newly screened holins proved to pore and to produce ghosts from Gram-positive bacteria.

• In the last 5 years, ghost-vaccines proved themselves at the production of potent vaccines, contraceptives, cellular and therapeutic vaccines. The research trend ensures further coming developments on the levels of lysing all types of microbial cells, expressing much more human and veterinary antigens, and maximizing the productivity and safety of ghost-vaccines. Yet, the out-of-the-box ideas to screen for new lysing genes, to optimize the use of a universal platform-ghost, and to investigate the potency of microbial carcass are still available.

Acknowledgments

The authors would like to express their great appreciation for their mentors Professor Amr A. Amara (Ph.D.) and Professor Francis O. Eko (D.Sc.); respectively. Simultaneously, a sincere appreciation is dedicated to Mr. Karriem Shabazz, Instructor at the American Embassy Language Center in Damascus; to Dr. Joseph Ansourian, free pharmacist; to Ms. Tara Douglas-Williams (MSLS) from M. Delmar Edwards M.D. Library at Morehouse School of Medicine for volunteering to edit the text of the manuscript, and to Professor Winfield Ward Murray, Instructor at Morehouse College and the Deputy Chief of Staff of Atlanta’s Mayor.

Author contribution statement

A M Batah: Investigation, Resources, Writing-Review & Editing; T A Ahmad: Conceptualization, Investigation, Writing-Original Draft, Writing-Review & Editing.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.