Abstract
Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses.
Highlights
Vaccination is the most effective medical intervention to prevent the spread of infectious diseases [1]
The aim of this study was to test the hypothesis that oral delivery of the whole protein, CD0873, on liposomes resembling its display on bacterial membranes could induce a more effective antibody response than CD0873 alone
The B cell receptor (BCR) must recognise its cognate antigen, and recognition is most effective if the antigen is encountered in its native form and is membrane-bound [37,38,39]
Summary
Vaccination is the most effective medical intervention to prevent the spread of infectious diseases [1]. Aside from the harmful pathogenic material they contain, live vaccines can undergo spontaneous mutations and revert to their infectious form, risking infecting the host [5,6]. To overcome this problem, efforts are focused on identifying individual antigens capable of safely eliciting immunoprotection [7]. A small number of adjuvants have been approved for injected vaccines, including aluminium salts, monophosphoryl lipid A, squalene-based oil-in-water emulsions and virosomes [10] Of these adjuvants, alum salts are the most widely used; their immunostimulatory activity can be weak, and formulations containing alum cannot be stabilised by freeze-drying [11]
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