T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

摘要

, Schematic representation of immunization groups (Grp) and regimens. The arrows (color coded as indicated) denote when various immunizations were given, with the time in weeks also recorded. , , Anti-trimer IgG- and IgA-binding antibodies measured in serum and vaginal secretions of vaccinated animals collected at the indicated time points. The asterisks represent significant differences between the groups at a time point as measured by Mann–Whitney rank-sum test (two-tailed, *  50, half-maximum effective concentration. , Serum nAb ID titers to BG505.T332N pseudovirus. The asterisks represent statistically significant differences between time points as measured by a Wilcoxon matched-pairs signed-rank test (two-tailed, *  P P e, A line plot to compare the magnitude of autologous nAb ID titers between SOSIP/3M-052 and HVV + SOSIP/3M-052 groups. The violin plots on the right show the distribution of responses at 2 and 4 weeks after the last SOSIP/3M-052 immunization (at weeks 82 and 84). Each symbol represents an individual animal and the median values are indicated by black dotted horizontal lines. The 25th and 75th percentiles are indicated by the colored (red or blue) dashed lines. , Flow cytometry plots representing Gag-CM9 tetramer and Ki67 expression by CD8 T cells (gated as live CD3 CD8 singlets) in blood collected at time points indicated on the top. Data from the three Mamu-A*01 animals in the HVV + SOSIP/3M-052 group are shown. , Gag-specific CD8 and CD4 T cell responses measured in blood at the time points (baseline, 1 week after each vaccination and 8 weeks before challenge) indicated on the axis are plotted. The percentage Gag-specific IFN-γ response was calculated by subtracting the frequency of IFN-γ T cells in the DMSO-treated cells from the values recorded after stimulation with the Gag peptide pool. In – , sample sizes were  = 15 per group at all time points, except week 82; at week 82,  = 13 in the SOSIP/3M-052 group because serum could not be collected from two animals. In box plots, each symbol represents an animal. The box shows median, upper and lower quartiles. The whiskers show 5th to 95th percentiles. Red and blue colors indicate immunization groups 1 and 2, respectively.