Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination

“…For example, we showed that early BOT class antibodies were inferior to GH-binding antibodies in that they disappeared from immune complexes at higher Fab concentrations than GH class antibodies, and this property did not change throughout the course of the immunization. Overall, our findings were consistent with and extend those of previously published rabbit-immunization studies ( de Taeye et al., 2015 , Klasse et al., 2016 , McCoy et al., 2016 , Sanders et al., 2015 , Torrents de la Peña et al., 2017 , Torrents de la Peña et al., 2018 ). Moreover, we also corroborated our nsEM data with occupancy data determined by a different, biochemical method.…”

“…All are key features to be considered in vaccine design. Our findings add substantially to earlier reports of sporadic neutralization of heterologous tier 2 viruses elicited in RMs by SHIVs bearing lab-adapted or animal-passaged HIV-1 Envs (61)(62)(63)(64) or Env immunogens (65)(66)(67)(68)(69)(70)(71)(72). The current results, together with a recent report by Wang and colleagues (73), show how closely neutralizing antibody responses in RMs can mirror responses in humans and indicate the extent to which protective responses elicited by reverse engineered or lineage-based vaccines in RMs might be expected to predict human responses to candidate vaccines (10,11,74,75).…”

“…Importantly, when diversity was clustered in immunogenic regions but more conserved regions were preserved, neutralizing antibodies may have been directed toward these conserved epitopes. While these observations are based on only a few individuals, these data are consistent with and extend preclinical data from the immunization of animals with immunogen cocktails (2, 3). Taken together, they suggest that the coadministration of multiple stabilized Env trimers with diversity introduced in key regions, along with parallel strategies to reduce the immunodominance of strain-specific epitopes, may represent one path to a cross-neutralizing antibody response.…”