A baculovirus-conjugated mimotope vaccine targeting Mycobacterium tuberculosis lipoarabinomannan

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a major cause of morbidity and mortality worldwide. However, an effective vaccine for M. tuberculosis is lacking. We panned a phage display library using monoclonal antibodies against M. tuberculosis liporabinomannan (LAM), an important component of the M. tuberculosis cell wall, and identified two peptide sequences, HSFKWLDSPRLR or SGVYKVAYDWQH, with high antibody affinity after multiple rounds of panning. Only the HSFKWLDSPRLR peptide induced an anti-LAM response when conjugated to either keyhole limpet hemocyanin (KLH) or to the baculovirus Autographa californica multicapsid nucleopolyherovirus (AcMNPV) when introduced into mice by injection or via intranasal inoculation, respectively. Vaccination with AcMNPV conjugated HSFKWLDSPRLR peptide delayed mortality in a mouse model of tuberculosis. Thus, we report a proof of principle M. tuberculosis vaccination strategy combining an anti-LAM mimotope with a baculovirus delivery system.