Long trimer interval reduces plasma anti-base responses in trimer-only immunized NHPs but does not enhance neutralizing activity
For all regimens, NHP plasma at three key time points of two weeks after the first, second, and third trimer immunizations were analyzed. Red circles and lines represent NHPs from short-interval group, and black circles and lines represent NHPs from long-interval group.
(A) Immunization regimen of short-interval and long-interval NHPs in trimer only immunization. Six NHPs were immunized with BG505 DS-SOSIP at weeks 0, 8, and 24 with S.Q (long interval), while five NHPs were immunized with BG505 DS-SOSIP at weeks 0, 4, and 16 with I.M. (short-interval). Both groups used Alum as adjuvant.
(B) Plasma response to BG505 DS-SOSIP trimer at three key time points.
(C) Total trimer response as measured by ELISA BG505 DS-SOSIP AUC values.
(D) Comparison of the total ELISA OD450nm values for binding to BG505 DS-SOSIP with (hollow circles) and without (solid circles) competition with RM19R Fab between the short and long interval groups at dilutions of 1:20, 1:500, and 1:500 for the three time points, respectively. Two-tailed paired-t test were used for statistical analysis to assess p values with and without Fab competition, with mean ± SEM. (E) Percentage of trimer response targeting the base region calculated from the values in D. The percentage was calculated by taking the difference between OD450 values without and with RM19R Fab, divided by the OD450 values without RM19R Fab blocking, and multiplied by 100.
(F) Plasma binding to glycan-base BG505 DS-SOSIP trimer, which has glycans added on the base region.
(G) Plasma responses as measured by glycan-base BG505 DS-SOSIP trimer AUC from F.
(H) Neutralizing ID50 on BG505 and MW965 at two weeks post third trimer immunization.
(I) Anti-V3 peptide response at two weeks post third trimer immunization. Two-tailed Mann-Whitney nonparametric tests were used for statistical analysis for D-I, to assess p values for mean ± SEM. ∗: p < 0.05; ∗∗: p < 0.01; ∗∗∗: p < 0.001; ∗∗∗∗: p < 0.0001; ns, not significant. The data in C represent two independent experiments with similar results.
See also Figures S1–S3.