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. 2021 Nov 23;9(12):2414. doi: 10.3390/microorganisms9122414

Figure 5.

Figure 5

Immune responses of mice to effective phage-based vaccine candidates and controls. (A) Timelines for the subset of vaccination studies shown in this figure (timelines and additional study details are also included in Table 2). Each study begins with a prime inoculation (green circle) and was followed by a cheek bleed (red drop) at Week 3, but subsequent boost (blue square) and bleed schedules differed between studies as indicated. Large red drops indicate cheek bleeds for which corresponding data are shown in panels B and C, while ELISA data for cheek bleeds indicated with small red drops are not shown here. (B) IgG ELISA curves for phage-coated (φ), spike-coated (S), and uncoated (ctrl) wells are shown for a selection of responsive animals immunized with recombinant phages and control samples. The Study # for each dataset is indicated above each panel. BaDAS-1 and DEaDAS-1 (central two panels) both induce strong IgG responses to the phage moiety (e.g., phiTM45; circle symbols) and somewhat weaker response to Spike protein (triangle symbols) in these animals, in both homologous and heterologous regimens. Spike protein, but not RBD (both with LPS adjuvant), induce an IgG response (right panel) to Spike, but no response to the phage. Mock immunization with parent phage phiTM45 induces strong IgG responses to the phage but no response to Spike protein, while PBS immunization does not induce IgG responses to either (left panel). (C) Reciprocal serum endpoint titers of all inoculated animals for vaccine regimens represented in panel B. Top and bottom panels show end point titers against Spike protein and phage phiTM45, respectively. Titers for individual animals are shown as diamond symbols (with whiskers extending to the minima and maxima of each dataset) and box boundaries mark the first and third quartiles of the data. Black and yellow lines are the mean and median endpoint titer, respectively. Shaded to indicate responses after primary inoculation (gray) or the boost (red), with collection times as shown in panel A.