Abstract
Abstract A promising direction of HIV-1 vaccine research has been eliciting fusion peptide (FP)-directed broadly neutralizing antibodies. To investigate if a potent FP-directed neutralizing response could be induced, 10 macaques were infected with simian-human immunodeficiency virus (SHIV) after immunization via FP priming and envelope trimer boosting. While the FP-directed neutralizing responses for some of the macaques dramatically increased within 8 weeks of SHIV infection, another macaque, JC69, displayed a potent cross-clade neutralizing response that grew in magnitude in the year following experimental SHIV infection. To characterize the immune response in JC69, anti-FP and -trimer ELISA, FP competition neutralization, and FP-specific B cell phenotyping analyses were performed longitudinally. FP-directed neutralizing response remarkably increased from week 32 to 68 post-SHIV infection and remained high until week 136. Furthermore, the proportion of FP-specific B-cells greatly expanded from week 32 to 68 post-SHIV infection. Overall, a potent cross-clade FP-directed neutralizing response was elicited in JC69 that peaked more than 1 year after SHIV infection. To better understand the mechanism of this late response, future directions will include the characterization of FP-directed monoclonal antibodies and viral RNA sequencing to map antibody-SHIV coevolution. Immunization to elicit site-specific neutralizing antibodies may be a key component of effective HIV vaccine strategies.
Published Version
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