Parenterally Administered Norovirus GII.4 Virus-Like Particle Vaccine Formulated with Aluminum Hydroxide or Monophosphoryl Lipid A Adjuvants Induces Systemic but Not Mucosal Immune Responses in Mice

Figures

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  Figure 1. NoV GII.4-specific systemic IgG (a, b) and IgA (c, d) antibody responses after IM immunization with 0.3 or 10 μg of NoV GII.4 VLPs alone or 0.3 μg of VLPs combined with Al(OH)3 or MPLA, or IN immunization with 10 μg of VLPs alone. Group mean OD490 values with standard error of the means of IgG (a) and IgA (c) antibodies in 1 : 200 (a) and 1 : 20 (c) diluted sera of experimental mice. Control mice received PBS only. End-point titers of IgG (b) and IgA (d) antibodies in sera of the experimental groups. Bars represent reciprocal of log10 geometric mean titers with 95% confidence intervals. The number of positive/tested mice is denoted on each figure in parenthesis.

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  Figure 2. Development of IgG (a) and IgG subtype antibodies (b, c) in mice immunized IM with 0.3 μg of GII.4 VLPs formulated with Al(OH)3 or MPLA or 10 μg of GII.4 VLPs alone. (a) Kinetics of NoV GII.4-specific total IgG antibodies in sera of mice immunized with the antigenic formulations at study weeks 0 and 3. Control mice received PBS only. Group mean OD490 values with standard error of the means of individual tail blood samples collected at indicated study weeks and termination sera at week 5 are shown. End-point titrations of anti-GII.4 IgG1 (b) and IgG2a (c) antibodies in termination sera at week 5. Mean titration curves with standard errors of the mean of the experimental groups are shown.

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  Figure 3. NoV GII.4-specific fecal antibody responses after IM immunization with 0.3 or 10 μg of NoV GII.4 VLPs alone or 0.3 μg of VLPs combined with Al(OH)3 or MPLA, or IN immunization with 10 μg of VLPs alone. End-point titrations of anti-GII.4 IgG (a) and IgA (b) antibodies in 10% fecal suspensions of experimental mice. Control mice received PBS only. Mean titration curves with standard errors of the mean of the experimental groups are shown.

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  Figure 4. Mucosal antibody responses in nasal washes after IM immunization with 0.3 μg of NoV GII.4 VLPs formulated with Al(OH)3 or MPLA, or IM or IN immunization with 10 μg of VLPs alone. End-point titrations of anti-GII.4 IgG (a) and IgA (b) antibodies in nasal washes (NWs) of experimental mice. Control mice received PBS only. Mean titration curves with standard errors of the mean of the experimental groups are shown.

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  Figure 5. IgG and IgA antibodies in cells from mesenteric lymph nodes after IM immunization with 0.3 μg of NoV GII.4 VLPs formulated with Al(OH)3 (a) or MPLA (b). End-point titration curves of anti-GII.4 IgG and IgA antibodies in cell culture supernatants from pooled mesenteric lymph nodes (MLNs) of experimental groups stimulated in vitro with 5 μg GII.4 VLPs. Control mice received PBS only.