Abstract
Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4+ T cell response, evident by the detection of effector CD4+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.
Highlights
Bacille Calmette-Guerin (BCG) is the only available vaccine for the prevention of tuberculosis [1] and has been given to over 3 billion individuals, making it the most widely administered vaccine to date
Due to the success of BCG in reducing childhood TB, and its proven safety record, strategies to develop a more effective TB vaccine have focused on improving the efficacy of BCG, either through the development of recombinant BCG strains and attenuated Mycobacterium tuberculosis (Mtb) vaccine strains or through the development of subunit and virus-vectored vaccines that can be used as a boost for BCG [7]
Oral delivery of live BCG using a lipid formulation has been shown to be effective at protecting animals against a virulent mycobacterial challenge [12,14,15,39]; the immune response elicited by this vaccine had not been fully investigated
Summary
Bacille Calmette-Guerin (BCG) is the only available vaccine for the prevention of tuberculosis [1] and has been given to over 3 billion individuals, making it the most widely administered vaccine to date. Due to the success of BCG in reducing childhood TB, and its proven safety record, strategies to develop a more effective TB vaccine have focused on improving the efficacy of BCG, either through the development of recombinant BCG strains and attenuated Mycobacterium tuberculosis (Mtb) vaccine strains or through the development of subunit and virus-vectored vaccines that can be used as a boost for BCG [7]. It has been shown that oral delivery more effectively targets the mucosal immune response than intradermal vaccination [9]. This is critical, given that the primary site of TB infection is the lungs
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