Intranasally administered anti-<i>Brucella</i> subunit vaccine formulation induces protective immune responses against nasal <i>Brucella</i> challenge

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>The present study was aimed to develop a safe and effective anti-<I>Brucella</I> subunit vaccine for mucosal protection against the respiratory exposure of <I>Brucella</I> infection. A chitosan-based <I>Brucella</I> nasal vaccine (BNV) was formulated using well-known <I>Brucella</I> immunogens, sodC, omp19, BLS and PrpA and tested against nasal <I>Brucella</I> challenge in BALB/c mice. The mice were intra-nasally vaccinated with sterile phosphate buffer saline (PBS), BNV or BNV plus <I>Brucella</I> LPS, and humoral (systemic IgG and mucosal IgA) and cell-mediated immune responses were analyzed. Results showed that mice vaccinated with either BNV or BNV plus LPS elicited significantly (p < 0.05) high IgG and IgA responses compared to the PBS control. The IgG responses were significantly (p < 0.05) higher than IgA levels, which showed almost comparable levels observed in either intestines or in lungs. Furthermore, the IgG and IgA responses against each individual component of the BNV formulation indicated that omp19 induced highest levels of both IgG and IgA levels than the other constituents of BNV formulation. Upon re-stimulation of the splenocytes with <I>Brucella</I> whole cell lysate, significantly (p < 0.05) high IFN-γ levels, lymphocyte proliferation, and CD4<SUP>+</SUP> T cell responses were observed in mice vaccinated with BNV or BNV plus LPS. Upon sub-lethal nasal challenge with wild-type <I>Brucella strain</I>, vaccinated mice showed significant reduction of <I>Brucella</I> recovery in lungs and spleen compared to the PBS control. This study indicates that BNV formulation with or without <I>Brucella</I> LPS efficiently induced humoral and cell-mediated immune responses and conferred significant protection against the sub-lethal <I>Brucella</I> challenge.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Development of a safe and effective mucosal vaccine for <I>Brucellosis</I>. </LI> <LI> A chitosan-based vaccine was formulated using <I>Brucella</I> immunogens, sodC, omp19, BLS and PrpA. </LI> <LI> Highly conserved Brucella antigens was able to give significant protection against the nasal challenge. </LI> </UL> </P>