The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice

Abstract

BackgroundIn some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.Methodology/ Principal FindingsImmunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen–specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.Conclusions/SignificanceThe mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans

“…Antigen-specific ELISA’s were performed to measure IgM and IgG1 levels in immunized C57BL/6J and AID -/- mice. We tested only IgG1 as this was the dominant antibody subclass induced in the alum-adjuvanted vaccines [7]. Immunized C57BL/6J and AID -/- mice developed antigen-specific IgM responses, with responses in immunized AID -/- mice equivalent to those seen in C57BL/6J mice.…”

“…Both antigens were shown to elicit protection in a mouse model of O . volvulus infection with third-stage larvae (L3) [6, 7]. Similarly, the Brugia malayi orthologous antigens were protective in a B .…”

“…volvulus induced a protective mechanism that is dependent on IgE and eosinophils [12]. Protection in mice induced by immunization with alum-adjuvanted Ov -103, Ov -RAL-2 or Ov -103 co-administered with Ov -RAL-2 vaccines appeared to be associated with a multifactorial complex network of immune factors including specific antibodies, Th2 cytokines, chemokines, and possibly specific effector cells recruited by the chemokines such as neutrophils, monocyte/macrophages and/or eosinophils [7]. Naïve human neutrophils in the presence of polyclonal antibodies from sera samples of O .…”

Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection

“…9 Advax is an adjuvant derived from delta inulin, a polysaccharide found in the roots of plants of the Compositae family. 10,11 Advax adjuvant has shown high levels of efficacy in vaccines against respiratory syncytial virus, 11 West Nile virus and Japanese encephalitis virus, 12,13 influenza, [14][15][16] severe acute respiratory syndrome coronavirus, 17 Listeria, 18 onchocercosis 19 and anthrax, 20 amongst others, consistent with its having broad efficacy across viral, bacterial and parasitic vaccines. An advantage of delta inulin adjuvant is that it enhances both Th1 and Th2 T cell responses.…”

Randomized controlled trial demonstrating the benefits of delta inulin adjuvanted immunotherapy in patients with bee venom allergy

“…[33][34][35][36] Only when in this semicrystalline state, referred to as delta inulin or Advax adjuvant, does inulin acquire unique immunologic properties, including the ability to act as a potent vaccine adjuvant. 37 Advax adjuvant has been shown to boost both humoral and cellular immunity and enhance vaccine-mediated protection across a wide variety of viral, 20,38-41 bacterial, [42][43][44][45] and protozoan 46 antigens in multiple species, including human subjects. This was the first study to assess the human safety and efficacy of Advax when combined with an allergen used for immunotherapy.…”