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School of Biochemistry and Immunology

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About

Research Interests

Watch Prof Lavelle talking about his research below.

Press Releases:

Development and mechanisms of action of vaccine adjuvants

Vaccines represent the most significant scientific contribution to global public health over the past two hundred years. Adjuvants and delivery systems are essential to enhance immune responses induced by vaccines since in many cases the purified protective antigens are not strongly immunogenic when administered alone. Adjuvants are substances that when co-administered with vaccines can enhance the antigen-specific immune response. In the case of live attenuated and killed vaccines, the “adjuvants” are intrinsic to the microbe, comprising factors such as bacterial LPS, flagellae or unmethylated CpG motifs within the DNA sequence or viral nucleic acids. The explosion in knowledge concerning innate immunity in recent years has facilitated a more mechanistic approach to adjuvant research since it is now clear that a principal mode of adjuvant action is via the induction of innate immune responses.

Dendritic cells are the pivotal cell in the induction of primary T cell responses against pathogens and vaccines. Thus my laboratory has a particular interest in the instruction of T cell responses by adjuvant-modulated dendritic cells. This work encompasses fundamental aspects of leukocyte biology but has wide application in the fields of vaccination and immunotherapy.

My group works on a range of adjuvants but with a particular focus on particulates. The most widely used adjuvant in humans is ‘alum’, a generic term for aluminium salts, particularly aluminium hydroxide and aluminium phosphate. Despite being in use for almost 100 years, the mechanism of action of alum is not fully understood. However, recent studies have shone new light on this and it is now clear that alum interacts specifically with elements of the innate immune system to direct B and T cell responses. Alum is not optimal for all vaccines and not suitable for mucosal administration so a range of alternatives are under investigation in the laboratory. We are studying the activation of immune responses by a range of other particulates including poly (lactide-co-glycolide (PLG)) and chitosan microparticles, emulsions and liposomes. Our recent data indicate that like alum, these can activate innate immune responses and significantly modulate host T cell and antibody responses. There are a number of key unresolved issues relating to the use of nano- and microparticles as adjuvants which we are currently addressing in collaboration with our academic and industrial collaborators. Specifically we are investigating the relationship between particle characteristics including size, shape and composition on their capacity to induce and direct innate and adaptive immune responses. In addition to their implications for vaccine research, these issues are also of relevance to the wider nanoscience sector since our data suggest that the immune system is modulated to a significant degree by particulate materials. Therefore our basic research findings will have far reaching implications regarding the use of nanoparticulates for drug and vaccine delivery and as biomaterials.

Specific issues addressed in the Lavelle lab

  1. How do particulate vaccine adjuvants activate innate and adaptive immunity?
  2. Can we develop improved adjuvants for induction of cellular immunity?
  3. Can we develop systems to facilitate the induction of potent immunity following mucosal vaccination?
  4. Can we specifically target particulate adjuvants to particular immune cells to enhance cellular immunity?