Vaccine formulation design: challenges and opportunities

Abstract

The rise in activity and multi-faceted impact of infectious agents such as human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented increase in morbidity and mortality around the globe. The spread of infectious diseases at an alarming rate has led to accelerated research on vaccine therapeutics, which can be further exemplified with COVID (coronavirus disease) vaccine development as a global emergency. This review aims to provide insights into vaccine development, components, manufacturing processes, types/platforms and strategies to improve their efficacy. The development of vaccines comprises four stages: (1) exploratory and preclinical, (2) clinical, (3) approval and (4) manufacturing and post-marketing surveillance. Vaccine formulations comprise antigens, adjuvants, preservatives, stabilizers, antibiotics, diluents and trace components. Vaccine manufacturing is a multi-step process involving antigen generation, release, purification, addition of other ingredients (e.g., adjuvants, preservatives, stabilizers, etc.), quality control testing and filling. Conventional vaccine platforms include live attenuated, inactivated/killed, toxoid, polysaccharide and polysaccharide conjugate, synthetic peptide and virus-like particles. Advanced technologies include viral vectors, bacterial vectors, DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) vaccines. These platforms provide rapid development of vaccines at a relatively low cost compared to conventional counterparts. Several approaches have been adopted for improving vaccine efficacy such as the inclusion of adjuvants and delivery of vaccines via mucosal and transcutaneous routes. Efficient uptake of vaccine antigens by microfold cells (found in the epithelium covering mucosa-associated lymphoid tissues) with subsequent transfer to the underlying antigen-presenting cells provides an efficient vaccine delivery route. In the case of the transcutaneous route, abundant antigen presenting cells found in the skin layer (e.g., Langerhans) ensure efficient vaccine delivery and induction of potent immune responses. Additionally, both these routes can overcome limitations associated with traditionally employed parenteral routes, such as risk of disease transmission in unhygienic conditions and reuse of contaminated needles, production of biohazardous waste, requirement of trained personnel for administration, invasiveness and poor patient compliance. Identification of conserved pathogenic sequences using advanced genetic engineering methods, machine learning, and artificial intelligence can help in developing efficient vaccines. Moreover, global partnerships, funding and provision of resources from the World Health Organization (WHO) can ensure vaccine development, testing and research activities for developing countries.