Studies in animal models are essential prerequisites for clinical trials of candidate HIV vaccines. Fc-independent and Fc-dependent functions of rabbit antibodies can be measured with commonly used assays; however, the ability of immunogenicity studies performed in rabbits to predict responses in RM will vary depending on the particular immune parameter of interest. IMPORTANCE Nonneutralizing antibody functions have been associated with reduced infection risk, or control of virus replication, for HIV-1 and related viruses. It is therefore critical to evaluate development of these responses throughout all stages of preclinical testing. Rabbits are conventionally used to evaluate the ability of vaccine candidates to safely elicit antibodies that bind and neutralize HIV-1. However, it remained unexplored how effectively rabbits model the development of nonneutralizing antibody responses in primates. We administered identical HIV-1 vaccine regimens to rabbits and rhesus macaques and performed detailed comparisons of vaccine-induced antibody responses. We demonstrated that nonneutralizing HIV-specific antibody responses can be studied in the rabbit model and have identified aspects of these responses that are common, and those that are unique, to rabbits and rhesus macaques. Our findings will help determine how to best utilize preclinical rabbit and rhesus macaque models to accelerate HIV vaccine candidate testing in human trials. = 0.004) and RM (Fig. 2B, week 8, Wilcoxon = 0.016) than those observed following i.n. priming. Titers of gp120-specific IgG increased following the first and second protein boost in both groups, and no differences were observed between vaccine groups 3 weeks after completion of the vaccine regimens (week 19, Fig. 2A and ?andB,B, Wilcoxon = 0.256 and = TUG-770 0.314, respectively). Due to the similarity between groups at the end of the regimen, we next combined group TUG-770 results as an overall assessment of the vaccine-induced antibody response that we then used to make comparisons across species. Importantly, following completion of the vaccine regimens, we observed no difference in the titers of vaccine-induced gp120-binding antibodies (Fig. 2C) or neutralizing antibody 50% inhibitory dilution (ID50) against subtype C tier 1a virus isolate MW965.26 (Fig. 2D) and tier 1b isolate 664.v2.c33 (Fig. TUG-770 2E) between rabbits and RM. Collectively these data indicate that the TUG-770 vaccines used in our study induced similar gp120-binding and neutralizing antibody responses in rabbits and RM. Open in a separate window FIG 1 Vaccination groups and study schedule. (A) Systemic (i.m./i.m.) and mucosal (i.n./i.m.+i.n.) vaccine regimens used for immunization of New Zealand White rabbits and rhesus macaques. (B) Schedule of vaccine administration and blood collection. Open in a separate window FIG 2 Antibodies capable of binding to gp120 and neutralizing tier 1 viruses were elicited in both rabbits and rhesus macaques (RM). ELISAs were used to measure titers of vaccine-elicited antibodies specific for the 1086.C gp120 protein used as a vaccine immunogen in sera from rabbits (A) and RM (B). (C) No differences (Wilcoxon rank sum test) in anti-Env IgG titers were observed between rabbit and RM sera collected 3 weeks after completion of the vaccine regimens (week 19). Titers of antibodies able CIT to neutralize the tier 1a virus isolate MW965.25 (D) and tier 1b isolate TUG-770 6644.V2.c33 (E) were similar (Wilcoxon rank sum test) in rabbit and RM sera collected 3 weeks after completion of the vaccine regimens (week 19). Open symbols represent animals that received the systemic i.m./i.m. vaccine regimen, and filled symbols represent animals that received.