Potential Impact of Food Safety Vaccines on Health Care Costs.

Foodborne pathogens continue to cause several outbreaks every year in many parts of the world. Among the bacterial pathogens involved, Shiga toxin-producing Escherichia coli, Campylobacter jejuni, and nontyphoidal Salmonella species cause a significant number of human infections worldwide, resulting in a huge annual economic burden that amounts to millions of dollars in health care costs. Human infections are primarily caused by the consumption of contaminated food. Vaccination of food-producing animals is an attractive, cost-effective strategy to lower the levels of these pathogens that will ultimately result in a safer food supply and fewer human infections. However, producers are often reluctant to routinely vaccinate animals against these pathogens since they do not cause any detectable clinical symptoms. This review highlights recent approaches used to develop effective food safety vaccines and the potential impact these vaccines might have on health care costs.

Analysis of resistance to antimicrobials and presence of virulence/stress response genes in Campylobacter isolates from patients with severe diarrhoea.

Campylobacter infections are a major cause of diarrhoea world-wide and two of the antimicrobials used for their control (erythromycin and ciprofloxacin) have been losing efficacy in recent years. In a sample of 174 genotyped isolates from the stools of patients with severe diarrhoea in Qatar, collected between 2005 and 2012, 63.2% showed resistance to ciprofloxacin, 8.6% to erythromycin, 0.57% to chloramphenicol and all were sensitive to gentamycin. While 33.9% of isolates were sensitive to all four antimicrobials, 59.8% were resistant to at least one, 6.3% were resistant to two and none showed resistance to three antimicrobials. There was no host sex- or age-dependence among isolates resistant to ciprofloxacin and erythromycin and no significant variation was found with the region of origin of the patients. All isolates were screened for the presence of 3 virulence factors (ciaB, cadF and cdtB) and two stress-response factors (htrB and clpP), all of which were present in more than 50% of the isolates. Host sex-, age- and region of origin-dependent variations in prevalence were found for some of these factors. Data analysis for the combination of virulence factors and their effect on antimicrobial resistance indicated that the prevalence of resistance to both erythromycin and ciprofloxacin was higher in isolates harbouring ciaB but not clpP. Prevalence of resistance to ciprofloxacin was similar in clpP positive and negative isolates also possessing htrB, while for htrB-negative isolates prevalence was higher in the absence of clpP. These results are discussed and their implications are highlighted.

Advances in vaccination against avian pathogenic Escherichia coli respiratory disease: potentials and limitations.

Avian pathogenic Escherichia coli (APEC) is one of the most economically devastating pathogens affecting the poultry industry. This group of extra-intestinal E. coli causes a variety of clinical conditions including airsacculitis and cellulitis. The economic impact of APEC is mainly due to mortality, slower growth rates, and carcass downgrading. In commercial broiler operations, APEC infections are controlled indirectly by vaccination against other respiratory diseases and minimizing stress conditions, and directly by administration of antimicrobial agents to suppress the infection in already infected flocks. The fact that most APEC strains possess some common virulence factors suggests that an effective vaccine against APEC is a viable option. The most important virulence factors that have been investigated over the years include type I and P fimbriae, aerobactin iron-acquisition system, and serum resistance traits. Despite the potential for developing an efficacious vaccine to combat this economically important poultry disease, several obstacles hinder such efforts. Those obstacles include the cost, vaccine delivery method and timing of vaccination as the birds should be immune to APEC by 21 days of age. Herein, we review the various attempts to develop an effective vaccine against the respiratory form of APEC diseases in poultry. We also discuss in-depth the potentials and limitations of such vaccines.

Delivery of immunogens to mucosal immune system using an oral inactivated cholera vaccine: a new approach for development of oral vaccines.

Oral vaccines have several attractive features; however, due to several challenges, to date, only a limited number of oral vaccines are licensed. Over the past two decades, several oral vehicle delivery systems have been developed to address these challenges and deliver antigens to the target cells in the mucosal immune system. While the size of vehicle delivery systems, the quantity of components in the vehicle formulation, the dose of administration, and even the type of animals species, are important aspects in development of a suitable oral vaccine, our results showed that entrapment of inactivated Vibrio cholera, a component in the structure of Dukoral vaccine into oral vehicle delivery systems, is able to induce a more rigorous humoral immune response in the systemic compartment. We further investigated the mechanism of Dukoral vaccine as a potential stimulator in induction of immune response by immunizing TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. We are hopeful that these findings will lead to development of more precisely-designed oral vaccines in the future.

An immunological comparison between lipidated and non-lipidated multivalent HIV-1 peptides representing Gp120 and Gag hypervariable regions.

Despite the extensive efforts towards development of an effective HIV vaccine, major challenges surrounding vaccine design still exist. We have previously developed a unique multivalent HIV-1 candidate vaccine representing hypervariable Gp120 and Gag regions. This candidate vaccine was able to induce a broad cell-mediated immune response in HLA-A2.1 mice and non-human primates against HIV-1 subtypes A-F. Herein, the reactivity of each hypervariable peptide mixture within our candidate peptide vaccine was further characterized to optimize the final vaccine formulation for the future clinical studies. The binding of each hypervariable region to sera from HIV-infected individuals demonstrated a strong reactivity between the antibodies and hypervariable regions. In addition, 15 groups of mice were immunized with adjuvant alone or each individual peptide mixture (lipidated or non-lipidated) to evaluate the ability of each variable region to induce humoral and cellular immune responses against HIV-1. A reactive HIV-1 specific immune response was detected among the immunized groups; however, mice receiving the Gag hypervariable regions demonstrated the highest frequency of cell-mediated immune responses.

Mucosal HIV vaccines: a holy grail or a dud?

The mucosal immune system appears to be a major target of the HIV infection. Therefore, a strong pre-existing anti-HIV immune response in mucosal compartments might be able to prevent HIV infection. Conflicting views regarding the mechanisms of protection at mucosal sites, inferred by the contradictory results of mucosal vaccines in human clinical trials, attests to our lack of knowledge in understanding the human mucosal immune system. In this article, we briefly review the function of innate and adaptive immune responses and discuss current strategies and potential adjuvants in designing and delivering HIV vaccines through mucosal routes.