Safety assessment of adjuvanted vaccines: Methodological considerations

Abstract

Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines.

Keywords: AS, Adjuvant Systems; EMA, European Medicines Agency; FDA, United States Food and Drug Administration; HPV, human papillomavirus; US, United States; WHO, World Health Organization; adjuvant; adjuvant system; safety; surveillance; vaccine.

Figure 1.

Effects of the movement against whole-cell pertussis vaccines on coverage and on disease epidemiology in the United Kingdom and Wales. Reprinted from The Lancet, Vol. 351, Gangarosa EJ, Galazka AM, Wolfe CR, Phillips LM, Gangarosa RE, Miller E, Chen RT, Impact of anti-vaccine movements on pertussis control: the untold story, pages 356–61, Copyright (1998), with permission from Elsevier.

Figure 2.

Factors guiding assessment of adjuvanted vaccine safety:Characteristics of the target population influence initial pre-clinicalevaluations. These features, as well as the results of pre-clinical testing, guide the specific assessment of vaccine safety in clinical trials.

Figure 3.

Post-licensure safety assessments are planned based on results of clinical trials, trends identified through spontaneous reports of adverse events after vaccination and field experience with the vaccine.

Figure 4.

Factors potentially influencing the influence the benefit-risk profile of adjuvanted vaccines.