Selection of adjuvants for vaccines targeting specific pathogens

Abstract

Adjuvants form an integral component in most of the inactivated and subunit vaccine formulations. Careful and proper selection of adjuvants helps in promoting appropriate immune responses against target pathogens at both innate and adaptive levels such that protective immunity can be elicited. Areas covered: Herein, we describe the recent progress in our understanding of the mode of action of adjuvants that are licensed for use in human vaccines or in clinical or pre-clinical stages at both innate and adaptive levels. Different pathogens have distinct characteristics, which require the host to mount an appropriate immune response against them. Adjuvants can be selected to elicit a tailor-made immune response to specific pathogens based on their unique properties. Identification of biomarkers of adjuvanticity for several candidate vaccines using omics-based technologies can unravel the mechanism of action of modern and experimental adjuvants. Expert opinion: Adjuvant technology has been revolutionized over the last two decades. In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations.

Keywords: Adjuvants; immunity; mechanism of action; pathogen; systems vaccinology.

Figure 1.

Schematic representation to highlight the possible mechanism of action by which adjuvants exert their adjuvanticity. Adjuvants can serve as a depot that mediates recruitment of APCs or act as a delivery system to facilitate uptake of antigen by the APCs. Adjuvants may activate innate immune responses by signaling through cell surface CLRs (such as Dectin-1, Dectin-2, Mincle), cytosolic NLRs, cell surface TLRs, endosomal TLRs or cytosolic RIG-I and MDA5. Signaling via PRRs may lead to the activation of several transcription factors, which results in the production of pro-inflammatory cytokines, chemokines and type I IFNs. Secretion of chemokines due to adjuvants may also result in the recruitment and infiltration of more immune cells. Adjuvants can activate c-GAS that participates in the STING-mediated IRF3-type I IFN pathway. Adjuvants can enhance the expression of MHC and co-stimulatory molecules to mediate efficient presentation of antigen to naïve CD4⁺ T cells. Depending upon the class of adjuvant, cellular (Th1) and/or humoral (Th2) immune responses may be induced. Adjuvants also play important roles in GC reaction, affinity maturation and long-lived memory responses as a part of humoral immunity. APC: antigen presenting cell, CLR: C-type Lectin receptors, NLR: nod-like receptors, TLR: toll-like receptor; RIG-I: retinoic acid-inducible gene I, RLR: RIG-I-like receptor; IFN: interferon, c-GAMP: cyclic guanosine monophosphate-adenosine monophosphate, c-GAS: c-GAMP synthase, STING: stimulator of IFN genes, GC: germinal centre, PRR: pattern recognition receptor, DAMP: damage-associated molecular pattern, ROS: reactive oxygen species, LDH: lactate dehydrogenase, Abs: antibodies, NLRP3: NLR family pyrin domain containing 3, AIM2: absent in melanoma2, MyD88: myeloid differentiation primary response 88, TRIF: TIR-domain-containing adapter-inducing IFN-β, IRF: interferon regulatory factor, TIRAP: toll/interleukin-1 receptor domain-containing adapter protein, AP-1: activator protein 1, NF-κB: nuclear factor-κB, MAL: MyD88 adaptor-like, TRAM: TRIF-related adaptor molecule, MDA5: melanoma differentiation-associated protein 5, ER: endoplasmic reticulum, ICAM-1: intercellular adhesion molecule 1, NK: natural killer, CTL: cytotoxic T lymphocyte, MHC: major histocompatibility complex.