Therapeutic proteins such as antibodies constitute the most rapidly growing class of pharmaceuticals for use in diverse clinical settings including cancer, chronic inflammatory diseases, kidney transplantation, cardiovascular medicine, and infectious diseases. Unfortunately, they tend to aggregate when stored under the concentrated conditions required in their usage. Aggregation leads to a decrease in antibody activity and could elicit an immunological response. Using full antibody atomistic molecular dynamics simulations, we identify the antibody regions prone to aggregation by using a technology that we developed called spatial aggregation propensity (SAP). SAP identifies the location and size of these aggregation prone regions, and allows us to perform target mutations of those regions to engineer antibodies for stability. We apply this method to therapeutic antibodies and demonstrate the significantly enhanced stability of our mutants compared with the wild type. The technology described here could be used to incorporate developability in a rational way during the screening of antibodies in the discovery phase for several diseases.

Vaccination, despite being recognized as one of the most effective primary public health measures, is viewed as unsafe and unnecessary by an increasing number of individuals. Anxiety about vaccines and vaccination programs leading to vaccine hesitancy results from a complex mix of social and political influences, cultural and religious beliefs, the availability of and ability to interpret health and scientific information, and personal and population experiences of health systems and government policies. Vaccine hesitancy is becoming a serious threat to vaccination programs, and was identified as one of the World Health Organization’s top ten global health threats in 2019. The negative impact of anti-vaccination movements is frequently cited as one of the major reasons for rising vaccine hesitancy amongst the general public world-wide. This review discusses the various issues surrounding vaccine hesitancy and the anti-vaccine movement, starting with the definitions of vaccine hesitancy and the anti-vaccine movement in their early history and in the modern era, before discussing the key drivers of vaccine hesitancy, particularly across different regions of the world, with a focus on various countries with low-, middle-, or high-income economies with different socio-economic populations. The review concludes with the impact of vaccine hesitancy on herd immunity and social, psychological, and public health measures to counter vaccine hesitancy.

Monoclonal antibodies (mAbs) have become a cornerstone in the therapeutic guidelines of a wide range of solid tumors. The targeted nature of these biotherapeutics has improved treatment outcomes by offering enhanced specificity to reduce severe side effects experienced with conventional chemotherapy. Notwithstanding, poor tumor tissue penetration and the heterogeneous distribution achieved therein are prominent drawbacks that hamper the clinical efficacy of therapeutic antibodies. Failure to deliver efficacious doses throughout the tumor can lead to treatment failure and the development of acquired resistance mechanisms. Comprehending the morphological and physiological characteristics of solid tumors and their microenvironment that affect tumor penetration and distribution is a key requirement to improve clinical outcomes and realize the full potential of monoclonal antibodies in oncology. This review summarizes the essential architectural characteristics of solid tumors that obstruct macromolecule penetration into the targeted tissue following systemic delivery. It further describes mechanisms of resistance elucidated for blockbuster antibodies for which extensive clinical data exists, as a way to illustrate various modes in which cancer cells can overcome the anticancer activity of therapeutic antibodies. Thereafter, it describes novel strategies designed to improve clinical outcomes of mAbs by increasing potency and/or improving tumor delivery; focusing on the recent clinical success and growing clinical pipeline of antibody-drug conjugates, immune checkpoint inhibitors and nanoparticle-based delivery systems.

Influenza remains one of the major public health concerns because it causes annual epidemics and can potentially instigate a global pandemic. Numerous countermeasures, including vaccines and antiviral treatments, are in use against seasonal influenza infection; however, their effectiveness has always been discussed due to the ongoing resistance to antivirals and relatively low and unpredictable efficiency of influenza vaccines compared to other vaccines. The growing interest in vaccines as a promising approach to prevent and control influenza may provide alternative vaccine development options with potentially increased efficiency. In addition to currently available inactivated, live-attenuated, and recombinant influenza vaccines on the market, novel platforms such as virus-like particles (VLPs) and nanoparticles, and new vaccine formulations are presently being explored. These platforms provide the opportunity to design influenza vaccines with improved properties to maximize quality, efficacy, and safety. The influenza vaccine manufacturing process is also moving forward with advancements relating to egg- and cell-based production, purification processes, and studies into the physicochemical attributes and vaccine degradation pathways. These will contribute to the design of more stable, optimized vaccine formulations guided by contemporary analytical testing methods and via the implementation of the latest advances in the field.