Single administration vaccines: delivery challenges, in vivo performance, and translational considerations.

INTRODUCTION: With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs). AREAS COVERED: This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data. EXPERT OPINION: Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.

Acidic amino acids as counterions of ciprofloxacin: Effect on growth and pigment production in Staphylococcus aureus NCTC 8325 and Pseudomonas aeruginosa PAO1.

Antimicrobial resistance (AMR) is emerging as a global threat to public health. One of the strategies employed to combat AMR is the use of adjuvants which act to enhance or reinstate antimicrobial activity by inhibiting resistance mechanisms. However, these adjuvants are themselves not immune to selecting resistant phenotypes. Thus, there is a need to utilise mechanisms which are either less likely to or unable to trigger resistance. One commonly employed mechanism of resistance by microorganisms is to prevent antimicrobial uptake or efflux the antibiotic which manages to permeate its membrane. Here we propose amino acids as antimicrobial adjuvants that may be utilizing alternate mechanisms to fight AMR. We used a modified ethidium bromide (EtBr) efflux assay to determine its efflux in the presence of ciprofloxacin within Staphylococcus aureus (NCTC 8325) and Pseudomonas aeruginosa (PAO1). In this study, aspartic acid and glutamic acid were found to inhibit growth of both bacterial species. Moreover, a reduced production of toxic pigments, pyocyanin and pyoverdine by P. aeruginosa was also observed. As evident from similar findings with tetracycline, these adjuvants, may be a way forward towards tackling antimicrobial resistance.