Abstract
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.
Highlights
The clinical, social, and economic burden of tuberculosis remains high despite the recent World Health Organization (WHO) tuberculosis report indicating that progress has been made towards the global reduction of tuberculosis [1]
None of the peptides conjugated to keyhole limpet hemocyanin (KLH) were bound by the CS-35 mAb (Fig 1F–1J)
Using a LAM ELISA, we found that as with the in vitro assay, none of the vaccinations with KLH-conjugated mimotope peptides induced anti-LAM antibodies at an antibody dilution of 1:100, while the CS-35 mAb showed a strong response (Fig 1K)
Summary
The clinical, social, and economic burden of tuberculosis remains high despite the recent World Health Organization (WHO) tuberculosis report indicating that progress has been made towards the global reduction of tuberculosis [1]. About one-third of the world’s population is infected with Mycobacterium tuberculosis while nearly 9 million cases of active tuberculosis are reported annually. In 2015 there were an estimated 10.4 million new tuberculosis cases and 1.8 million tuberculosis deaths overall, including 1.0 million cases and 170,000 deaths among children [2]. The Bacillus Calmette Guerin (BCG) vaccine remains the only licensed vaccine for the prevention of tuberculosis.
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