Fig. 7: 10E8-GT immunogens induce 10E8-class responses in NHPs.
From: Vaccination induces broadly neutralizing antibody precursors to HIV gp41
a, Alignment of known rhesus macaque homologs of the human gene encoding DH3-3. Macaque D-gene residues that differ from the critical YxFW binding motif (orange) that directly contacts the 10E8 epitope are highlighted in red. b, HCDR3 length distribution for 10E8-GT10.2++10E8–GT10.2-KO– epitope-specific CD20+IgG– naive B cells sorted from unimmunized macaques (n = 9) compared to 10E8-GT10.2− nonbinding BCRs from the same macaques and the human naive BCRs, as in Fig. 4. c, Percentage of 10E8-class HCDR3s among CD20+IgG− naive B cells from unimmunized macaques (n = 9) compared to human naive BCRs from Fig. 4 (n = 3) and to rhesus macaque sequences from the Observed Antibody Space (OAS) repository (n = 8)49. d, Macaque immunization schedule for an escalating dose of 10E8-GT10.2 12mer (n = 8) or 10E8-GT12 12mer (n = 6), indicating analysis of lymph node fine needle aspirates (LN FNA) at weeks –2, 3 and 10 and analysis of blood at weeks 6 and 11 or week 10 for macaques immunized with 10E8-GT10.2 12mer or 10E8-GT12 12mer, respectively. e, Percentage of 10E8-class HCDR3s among 10E8-GT10.2++10E8-GT10.2-KO− or 10E8-GT12++10E8-GT12-KO− epitope-specific IgG+ BCRs from macaques after immunization as in d in the GCs and PBMCs at all time points indicated in d combined for each macaque compared to macaques immunized with stabilized soluble HIV Env50 (control) at weeks 3, 4, 7 and 10 after immunization. Open symbols represent macaques lacking a permissive DH3-41 allele; **P = 0.004. Data were analyzed by two-sided Mann–Whitney test. f, Percentage of 10E8-class VH among IgG+CD20+IgD− memory BCRs with 10E8-class HCDR3s or among IgG+ CD20+IgD− memory BCRs lacking the YxFW motif (non-10E8) from macaques after immunization as in d; *P < 0.05. Data were analyzed by Kruskal–Wallis test with a Dunn’s multiple comparison correction; control versus 10E8-class induced by 10E8-GT10.2 12mer, P = 0.03; control versus 10E8-class induced by 10E8-GT12 12mer, P = 0.02. g, Percentage of LN01-class HCDR3s among 10E8-GT10.2++10E8-GT10.2-KO− or 10E8-GT12++10E8-GT12-KO− epitope-specific IgG+ BCRs from macaques after immunization as in d; *P = 0.04. Data were analyzed by two-sided Mann–Whitney test. h, Crystal structure of a 10E8-GT10.2-induced macaque antibody with a YxIW motif from week 3 in complex with 10E8-GT10.2 (right) with the structure of 10E8 bound to peptide12 (left) shown for reference. Colors are as in Fig. 3.
