Comparison of anti-gp140 IgG responses induced by various HIV-1 repRNA constructs in mouse and rabbit models
Serum anti-gp140 IgG responses in (A) female C57Bl/6 mice (6–8 weeks old; n = 5/group) and (B) young adult female New Zealand White (NZW) rabbits (approximately 28 weeks old; n = 4/group) after receiving two doses 3 weeks apart. (A) Mice in each group were immunized by intramuscular injection with 1 μg of LION-formulated repRNA construct indicated on the vertical axis. Mice immunized with repRNA expressing Env FL, BG505 SOSIP.664-scfl, or Gag-IRES-Env were partially seropositive and advanced to rabbit immunogenicity study shown in (B). NZW rabbits were immunized by intramuscular injection with 100 μg or 50 μg of each candidate repRNA formulated with LION. Serum IgG responses in mice and rabbits against the BG505 SOSIP.664 gp140 recombinant protein were measured by ELISA. Individual and mean (SD) endpoint titers are shown. Mean endpoint titer from each group in (A) was log10 transformed and compared against the Gag group by ordinary one-way ANOVA and Dunnett’s multiple comparisons test. Mean endpoint titer from each group in (B) was log10 transformed and compared against every other group by ordinary one-way ANOVA and Tukey’s multiple comparisons test. Statistically significant differences in (A) are only shown for groups with at least one seropositive animal and in (B) only shown for each dose cohort. Summary of p values: ∗ < 0.05; ∗∗∗ < 0.001; ∗∗∗∗ < 0.0001.