ADMEProcesses in Vaccines andPK/PDApproaches for Vaccination Optimization

Abstract

In order to present the current knowledge on vaccine absorption, distribution, metabolism, and excretion (ADME) and vaccine modeling, this chapter briefly summarizes how vaccines are developed, what type of vaccines are available, and how much it is known about their mechanisms of action. It also summarizes the current knowledge on the impact of administration routes, dosing schedules, and formulation on vaccine ADME processes, focusing on the vaccine properties that can be altered without modifying the antigens (Ag). The chapter then describes the influence of biopharmaceutics properties on vaccine pharmacokinetic (PK) processes such as absorption and distribution. Mathematical models may be used to optimize vaccination in cancer treatment. There is an urgent need to perform studies based on PK, pharmacodynamics, and systems biology principles, to get the longitudinal information required, that once analyzed under the model‐based framework, can be linked to the biopharmaceutical characteristics of the vaccine formulation.

Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities

“…Understanding how novel adjuvants, excipients, and carrier systems, such as nanoparticles, bacterial ghosts, heat shock proteins, or other vesicles (see Table 1), influence the ADME of personalized TCVs may provide insights to improve efficacy and/or safety. 87,90,91 Additional aspects related to interactions and use in special populations should be considered in development of these novel modalities. [92][93][94] Immune Cell Responses as Surrogate Biomarkers for Efficacy Certain human immune cell functions allow for quantitative measurement of responses to personalized TCV therapy.…”

“…Obstacles to Determining an Optimal Dose and Regimen for a Personalized Therapeutic Cancer Vaccine Preclinical models used to inform on the best route of administration, adjuvant, carrier, dose, and schedule do not scale allometrically and may not translate across species103,105 d Limited understanding of vaccine ADME to allow optimization of biopharmaceutical properties90 …”

Preclinical Studies and Clinical Trials in Determination of Safety and Efficacy of Meningococcal Vaccines: Present Scenario

“…Rational vaccine development demands judicious selection of adjuvants to modulate immunological response [24,30,31]. For example, Freund's adjuvant exhibits depot effect prolonging vaccine release, thus strengthening immune response [24].…”

“…Certain vaccine antigens such as meningococcal serogroup A polysaccharide being acid-labile [29] cannot be delivered orally which necessitates the change of administration route or formulation design. Moreover, the role of biopharmaceutical variables such as particle size, selection of polymers, use of carriers such as liposomes and proteasomes as delivery systems may influence uptake by antigen-presenting cells and subsequent translocation to lymph node [24,30,31]. In vivo stability of the vaccine candidate should be properly assessed.…”

“…It is difficult to establish ability of vaccine to elicit immunogenic response without administering it to a biological system. Parameters such as seroconversion rates, geometric mean antibody titers [30] are characterized using animal models in vaccine development. Animal studies are crucial in verifying the outcomes of the in silico mathematical tools such as differential equation (DE) modeling, agent-based modeling, and systematic in silico screening approach with different filtering phases [30,40].…”