Abstract
It has recently been recognised that vaccine adjuvants play a critical role in directing the nature of a vaccine induced effector response. In the present study, several adjuvants were evaluated for their ability to protect sheep after field vaccination with the larval-specific Haemonchus contortus antigen, HcsL3. Using a suboptimal antigen dose, aluminium adjuvant was shown to reduce the cumulative faecal egg counts (cFEC) and worm burden by 23% and 25% respectively, in agreement with a previous study. The addition of Quil A to the aluminium-adjuvanted vaccine brought cFEC back to control levels. Vaccination with the adjuvant DEAE-dextran almost doubled the protection compared to the aluminium-adjuvanted vaccine resulting in 40% and 41% reduction in cFEC and worm counts compared to controls. Examination of skin responses following i.d. injection of exsheathed L3, revealed that cFEC was negatively correlated with wheal size and tissue eosinophils for the DEAE-dextran and aluminium-adjuvanted groups respectively. These studies have for the first time shown the potential of DEAE-dextran adjuvant for helminth vaccines, and discovered significant cellular correlates of vaccine-induced protection.
Highlights
The generation of natural immunity against gastrointestinal nematode (GIN) parasites, and helminth parasites in general, displays some unique characteristics compared to viral and bacterial infections, in particular in the recruitment and activation of ‘allergic’ or type-2 effector cells [1,2,3]
While helminth vaccines based on the ‘hidden antigen’ approach i.e. not boosted by natural immunity, may rely on high antibody titres [5], it is likely that vaccination strategies aimed at mimicking and accelerating natural immunity will require the induction of both cellular and humoral immunity including the induction of a type-2 effector response
In most cases of currently used adjuvant systems, the exact innate stimulation pathways are unknown and may not involve Toll-like receptors (TLRs) activation [6]. This is the case for the most commonly used aluminium adjuvants [14], as well as the two other adjuvants used in the present study, DEAE-dextran (DD) and Quil A
Summary
The generation of natural immunity against gastrointestinal nematode (GIN) parasites, and helminth parasites in general, displays some unique characteristics compared to viral and bacterial infections, in particular in the recruitment and activation of ‘allergic’ or type-2 effector cells (mast cells and eosinophils) [1,2,3]. Attempts to generate subunit vaccines against GIN parasites have in the past relied heavily on successes achieved with microbial vaccines, including the use of potent vaccine adjuvants that generate high antibody responses, the major correlates of protection in most existing vaccines [4]. While helminth vaccines based on the ‘hidden antigen’ approach i.e. not boosted by natural immunity, may rely on high antibody titres [5], it is likely that vaccination strategies aimed at mimicking and accelerating natural immunity will require the induction of both cellular and humoral immunity including the induction of a type-2 effector response. For helminth vaccines aimed at replicating natural immunity, a type-2 immune response may be essential to achieve protection. In a previous small pen trial, we observed that immunization with a purified, larval-specific surface antigen of H. contortus, was only protective when administered with the type-2 adjuvants, aluminium hydroxide and cholera toxin, while addition of pertussis toxin increased antibody titres but abrogated protection [8]
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