Novel Vaccine Candidates Induce Humoral and Cellular Immunity and Confer Protection Against Multidrug-Resistant Acinetobacter baumannii

Nouran Rezk (University College Dublin, Ireland)

16:59 - 17:02 Tuesday 03 November Afternoon

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Abstract

Acinetobacter baumannii causes life-threatening, multidrug-resistant hospital-acquired infections and is classified by the World Health Organisation as a “Critical Priority” pathogen with currently no licensed vaccines. Its ability to adopt both extracellular and intracellular lifestyles presents a major challenge for vaccine development. Bacterial proteins involved in host-cell attachment represent attractive vaccine candidates. This study evaluates the protective efficacy and immunogenicity of two novel vaccine candidates (AgD and AgB) in an acute pneumonia mouse model, identified based on their involvement in A.baumannii attachment to human lung epithelial cells. Mice immunised with SAS-adjuvanted AgD and subsequently challenged with A. baumannii acute pneumonia showed substantial reductions in both bacterial lung colonisation and spleen dissemination relative to controls (3.15- and 3.14-log₁₀ CFU/mg, respectively). AgD also induced high antigen-specific reciprocal endpoint titres of total IgG, IgG1, and IgG2c (5.5 log10), Inhibiting lung cell adhesion. Moreover, AgD-induced recall responses showed 18.1-fold induction of Interferon-γ (IFN-γ) compared with controls. Ongoing analysis will characterise the cellular immune profile that contributed to its protective capacity. An mRNA-AgD LNP formulation is also currently being evaluated in vivo to evaluate mRNA as a vaccine platform against A. baumannii. Splenocytes from AgB-immunised mice showed ~3-fold increases in IFN-γ–producing helper and cytotoxic T-cells; a 1.5-fold increase in IL-4–producing Th2 cells, with 1.4- and 1.8-fold increases in IL-17A– and IL-22–producing Th17 cells, respectively. An in vivo challenge study is underway to evaluate its protective efficacy. Overall, both antigens are promising vaccine candidates, eliciting protective humoral and cellular immunity against A. baumannii.

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