The Influence of MV130 immunotherapy on Nasal Colonisation in a Controlled Human Infection Model of Pneumococcal Carriage in Malawi

<ns3:p>Background <ns3:italic>Streptococcus pneumoniae</ns3:italic> is the leading cause of morbidity and mortality due to community-acquired pneumonia (CAP), bacterial meningitis, and bacteraemia worldwide. Pneumococcal conjugate vaccines (PCV) represent a great achievement in providing protection from invasive pneumococcal disease, but they are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and are less effective against mucosal infection (13–20%) than against invasive disease. We will use our Human Challenge Infection Model (CHIM) to test the effect of MV130, a mucosal bacterial immunotherapy, on pneumococcal colonization. MV130 is a sublingual preparation consisting of whole-cell heat inactivated bacteria strains namely V104 <ns3:italic>Streptococcus pneumoniae</ns3:italic> 60%, V101 <ns3:italic>Staphylococcus epidermidis</ns3:italic> 15%, V102 <ns3:italic>Staphylococcus aureus</ns3:italic> 15%, V113 <ns3:italic>Klebsiella pneumoniae</ns3:italic> 4%, V105 <ns3:italic>Moraxella catarrhalis</ns3:italic> 3%, and V103 <ns3:italic>Haemophilus influenzae</ns3:italic> 3%. The broad nature of activity against respiratory infections, long lasting immune response and safety profile makes MV130 an appealing option in preventing pneumococcal nasal colonisation and subsequent infection. We will recruit 100 participants with equal numbers randomized to either MV130 or placebo to investigate the innate and cellular immunological effects of M130 and its subsequent effect on pneumococcal nasal colonization. Participants will be enrolled in the study upon successful screening and consenting and will commence product administration and continue for up to 42 days prior to inoculation with experimental <ns3:italic>Streptococcus pneumoniae</ns3:italic> serotype 6B. The primary end point will be the neutrophil to T cell ratio at day 14 assessed in nasal cell samples. The secondary endpoint will be then nasal pneumococcal carriage rates at day 2 and 7 post-inoculation. Both the neutrophil to T cell ratio and the pneumococcal carriage rates will be compared between the MV130 and the Placebo group. This study will help us understand the efficacy of a polybacterial immunotherapy in preventing the transmission of <ns3:italic>Streptococcus pneumoniae</ns3:italic> and other related infectious agents and the prevention of subsequent infections caused by the same. Trial Registration <ns3:bold>Pan African Clinical Trial Registry (REF: PACTR202403820001276)</ns3:bold> <ns3:bold> <ns3:ext-link xmlns:ns4="http://www.w3.org/1999/xlink" ext-link-type="uri" ns4:href="https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25496">https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25496</ns3:ext-link> </ns3:bold> Clinical Trial dates <ns3:bold>28 March 2024.</ns3:bold></ns3:p>