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 postlicensure 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.

Immunization in pregnancy clinical research in low- and middle-income countries – Study design, regulatory and safety considerations

“…Baseline outcome rates are a useful part of such an assessment. There is little progress in determining baseline rates in LMIC settings of maternal and neonatal outcomes [4] , [9] , [10] , [11] .…”

“…This needs to be kept in mind while planning the timelines for enrollment and the attrition rates of the clinical trial or study. Insisting upon identifying, consulting and obtaining additional assent from key decision makers apart from the consent from the pregnant women prior to enrolment would be an easier option for the research team, but this would effectively disempower the woman from making decisions [11] , [12] , [20] .…”

“…In some countries, women less than 18 years of age can provide assent to enroll in a study while pregnant while consent for her participation would have to come from her parent or legal guardian. But the same women can give consent for her newborn after delivery [11] , [12] , [20] .…”

Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

“…Adjuvant is an option to strengthen and broaden NoV immune responses, and NoV vaccine candidate adjuvanted with aluminum hydroxide and monophosphoryl lipid A has been tested in phase IIb clinical trials [21]. However, due to the local and systemic adverse events associated with adjuvanted vaccines [22], our hypothesis is that in the pediatric NoV vaccine candidate we developed, extremely immunogenic VP6 protein may serve to substitute the external adjuvant. To this end, we have shown that RV VP6 in our combination vaccine has an adjuvant effect on NoV immune responses in vitro and in vivo [14,[23][24][25].…”

Rotavirus Inner Capsid VP6 Acts as an Adjuvant in Formulations with Particulate Antigens Only

“…While alum is employed mainly to adsorb the vaccine antigen and as a delivery system [ 21 , 22 ], it has also been described to have some immunomodulatory features [ 23 ]. However, because of the local and systemic adverse effects associated with adjuvanted vaccines [ 24 ], alternatives to current and potentially harmful adjuvants are being considered.…”