Adjuvants are substances that enhance the magnitude and durability of the antigen-specific immune responses upon vaccination . They include vehicles and immunostimulants, with some components sharing both properties.
– Vehicles are usually of particulate nature (e.g. aluminum hydroxide, emulsions) and they are mixed with the antigen before the administration of the vaccine. This generates a "depot effect" (e.g. intra-muscular), allowing the slow release of the antigen and longer interaction with the immune cells. Some vehicles also feature immunostimulatory properties, such as aluminum hydroxide (alum) which triggers the inflammasome response .
– Immunostimulants are usually synthetic molecules known to activate pattern recognition receptors (PRR), such as Toll-like receptors (TLR) . PRR agonists have the capacity to stimulate antigen-presenting cells (APC), resulting in the enhanced presentation of antigens as well as secretion of pro-inflammatory chemokines and cytokines. The mixing of the antigen and the PRR agonist aims at co-delivering both molecules to the same APC for a maximal T cell response.
– Antigen-adjuvant conjugates are antigen-PRR agonist fusion vaccines that elicit a stronger immune response than simple mixtures of antigen and adjuvant. This may be explained by overcoming the rapid dissociation of the two molecules after mixture administration. Additionally, conjugated antigens are taken up more efficiently by dendritic cells and can be internalized to form an intracellular antigen and immunostimulant depot for prolonged T cell stimulation .
InvivoGen adjuvants are VacciGrade™, a specific grade for preclinical studies. They are filled under strict aseptic conditions in a clean room. The absence of bacterial contamination is assessed by a sterility test using a pharmacopeia-derived assay. The level of bacterial contaminants (endotoxins and lipoproteins) in each lot is verified using a LAL assay and/or a TLR2 and TLR4 reporter assay.
VacciGrade™ Adjuvant Collection
InvivoGen provides the largest choice of vaccine adjuvants (for research use only).
Alum & emulsions – generate depots that trap antigens at the injection site for a sustained stimulation of the immune system through increased recruitment and activation of APCs.
PRR agonists – effectively activate a local innate immune response, predominantly targeting the APCs, and consequently influencing the necessary adaptive immune responses. Members of nearly all of the PRR families are potential targets for adjuvants.
Conjugatable PRR Ligands – can be chemically coupled to the antigen to achieve more potent immune responses when compared to those induced by antigen and adjuvant mixtures.
COVID-19 related research
The vaccine development effort in response to the COVID-19 pandemic is unprecedented in terms of both scale and speed. A number of different strategies are being explored for the development of a successful vaccine against SARS-CoV-2, most of them requiring the addition of an adjuvant to potentiate the efficacy and safety of the vaccine.
1. Pulendran, B. et al., 2021. Emerging concepts in the science of vaccine adjuvants. Nat Rev Drug Discovery. 20(6):454-475.
2. Xu, Z. & Moyle, PM., 2018. Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands. Bioconjugate Chemistry. 29(3):572-586.