Anti-Immunomodulation Vaccines
There is no human vaccine against parasitic worms. Helminths rely on suppressing immune responses, reducing their immunogenicity, and likely also rely on their body size such that it may be too damaging for the host itself to generate a response strong enough to kill the parasite.
Our working hypothesis is that given that parasites have evolved with immune responses of their hosts, a vaccine would need to counter the parasites adaptations to immune evasion.
The ability of such parasites to establish long-lasting infections – up to 40 years, maybe more – rests for a great part on their ability to suppress their host's immune response. We are interested in applying our understanding of this phenomenon to design 'smarter' vaccines. We have shown in the L. sigmodontis model that it is indeed possible to block these parasite factors and thereby to release the host's immune response from parasite-driven suppression. We hypothesise that a benefit of targeting only parasite-driven immune suppression is that it leaves the host's regulatory mechanisms intact, thereby reducing risks of inducing auto-immunity.
Phenotypic plasticity
Parasitic nematodes can alter life history traits in response to their host’s protective immune responses in a way that maximises their fitness. While studying parasite survival in vaccinated hosts, we discovered that Litomosoides sigmodontis grew faster, reproduced earlier and increased its fecundity in response to stronger immune responses (see here). We study parasite transmission as a function of host protective immunity and parasite survival and development. A central interest of our research is to assess the implications of phenotypic plastic responses of parasites in a world which is to transition to widespread vaccine coverage.
Two helminths are helping us address these questions. (i) The filarial nematode Litomosoides sigmodontis which the data suggest is capable of adaptive phenotypic plastic responses: when immune effectors are present at its site of infection, even if only transiently, it accelerates its development and increases the production of offspring. (ii) The flatworm Schistosoma mansoni which requires the presence of a T-cell immune response from its host in order to develop and mature normally.
The medical and epidemiological relevance of these phenomena are that a vaccine or any intervention that provides developmental signals to the parasites may worsen that disease burden in populations as they gain access to treatment.
Immunity and nutrition
As any other biological system, the immune system requires nutritional resources to function. Such needs are in maintaining the immune system's surveillance role, producing and replacing cellular and humoral elements, and in generating appropriate responses to pathogens. Protein, in particular, is needed for this. However, protein is also needed for other functions of the organism: growth, reproduction, lactation, etc. When protein is scarce, organisms will prioritise its allocation. How will the immune system perform in response to a helminth infection when resource is limiting? Will the immune response shut down, or will it adopt an alternative strategy? How do malnourished individuals respond to vaccination?
To begin to answer these questions, we are collaborating with Jos Houdijk at the Scottish Agricultural College.
Immunity in the Wild
Most of the research done on immune responses and vaccines are carried out in clean labs and on very narrow ranges of organisms exposed to limited diversity of pathogens. However, it has long been obvious that certain assumptions made in those settings may not easily apply to conditions in which organisms are widely variable genetically, are exposed to diverse multiple infections, variable nutritional resources, fluctuating climates and so on. Unfortunately, not much immunology is done on organisms living "in the wild" - for obvious technical and logistical reasons.
We are involved in trying to bridge part of that gap between ecologists and immunologists in two ways.
There is no human vaccine against parasitic worms. Helminths rely on suppressing immune responses, reducing their immunogenicity, and likely also rely on their body size such that it may be too damaging for the host itself to generate a response strong enough to kill the parasite.
Our working hypothesis is that given that parasites have evolved with immune responses of their hosts, a vaccine would need to counter the parasites adaptations to immune evasion.
The ability of such parasites to establish long-lasting infections – up to 40 years, maybe more – rests for a great part on their ability to suppress their host's immune response. We are interested in applying our understanding of this phenomenon to design 'smarter' vaccines. We have shown in the L. sigmodontis model that it is indeed possible to block these parasite factors and thereby to release the host's immune response from parasite-driven suppression. We hypothesise that a benefit of targeting only parasite-driven immune suppression is that it leaves the host's regulatory mechanisms intact, thereby reducing risks of inducing auto-immunity.
Phenotypic plasticity
Parasitic nematodes can alter life history traits in response to their host’s protective immune responses in a way that maximises their fitness. While studying parasite survival in vaccinated hosts, we discovered that Litomosoides sigmodontis grew faster, reproduced earlier and increased its fecundity in response to stronger immune responses (see here). We study parasite transmission as a function of host protective immunity and parasite survival and development. A central interest of our research is to assess the implications of phenotypic plastic responses of parasites in a world which is to transition to widespread vaccine coverage.
Two helminths are helping us address these questions. (i) The filarial nematode Litomosoides sigmodontis which the data suggest is capable of adaptive phenotypic plastic responses: when immune effectors are present at its site of infection, even if only transiently, it accelerates its development and increases the production of offspring. (ii) The flatworm Schistosoma mansoni which requires the presence of a T-cell immune response from its host in order to develop and mature normally.
The medical and epidemiological relevance of these phenomena are that a vaccine or any intervention that provides developmental signals to the parasites may worsen that disease burden in populations as they gain access to treatment.
Immunity and nutrition
As any other biological system, the immune system requires nutritional resources to function. Such needs are in maintaining the immune system's surveillance role, producing and replacing cellular and humoral elements, and in generating appropriate responses to pathogens. Protein, in particular, is needed for this. However, protein is also needed for other functions of the organism: growth, reproduction, lactation, etc. When protein is scarce, organisms will prioritise its allocation. How will the immune system perform in response to a helminth infection when resource is limiting? Will the immune response shut down, or will it adopt an alternative strategy? How do malnourished individuals respond to vaccination?
To begin to answer these questions, we are collaborating with Jos Houdijk at the Scottish Agricultural College.
Immunity in the Wild
Most of the research done on immune responses and vaccines are carried out in clean labs and on very narrow ranges of organisms exposed to limited diversity of pathogens. However, it has long been obvious that certain assumptions made in those settings may not easily apply to conditions in which organisms are widely variable genetically, are exposed to diverse multiple infections, variable nutritional resources, fluctuating climates and so on. Unfortunately, not much immunology is done on organisms living "in the wild" - for obvious technical and logistical reasons.
We are involved in trying to bridge part of that gap between ecologists and immunologists in two ways.
- In the search for a vaccine against filariasis, our effort is currently focused on collecting as much data as we can in murine, bovine and human filarial infections. The aim is to identify commonalities between these systems that explain or at least correlate with protection against filarial infections, and possibly use them to inform vaccine design. This work is done in collaboration with our African and European partners in the EU FP7 project "EPIAF".
- The longitudinal study of wild rodents in local woodland gives us the possibility to observe how immune systems prioritise between the various infections to which the animals are exposed, how these interact with individual health and how drug interventions shape these relationships. This work is being developed in collaboration with Amy Pedersen.