Self-amplifying RNA-based activation of HIV-1 broadly neutralizing antibody B cell precursors 2690

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Abstract Description Elicitation of broadly HIV neutralizing antibody (Ab) responses requires sequential immunizations with specifically designed HIV Env-derived proteins. Such constructs are presently in pre-clinical and clinical evaluation, but the production of multiple immunogens is costly, and the implementation of prolonged immunization regimes is difficult. An alternate approach is to utilize mRNA-based vaccine platforms. However, little is known about how the B cells and Ab responses elicited by mRNA-expressed HIV immunogens compare to those elicited by corresponding recombinant (rec) proteins. Here, we compared the B cell and Ab responses elicited by HIV immunogens delivered as adjuvanted (3M-052-AF + Alum) rec proteins or as self-amplifying mRNA (saRNAs). These immunogens aim to activate and initiate the maturation of VRC01-class B cells, that target the CD4-binding site (BS) on HIV-1 Env and reduce HIV acquisition in clinical testing. Both approaches resulted in comparable plasma Ab responses to the CD4-BS following prime immunization, and increased titers following the boost. This confirms that the proteins are immunogenic when administered via the saRNA platform. Moreover, saRNA immunization resulted in higher rates of somatic mutations in VRC01-class B cells than those achieved by the corresponding adjuvanted rec proteins. In sum, our study identifies a promising vaccine strategy that may allow accelerated clinical evaluation of bnAb-eliciting HIV-1 Env derived immunogens. Funding Sources IPCAVD (U19 AI174242) Topic Categories Vaccines and Immunotherapy (VAC)

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