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Arenavirus-Based Vectors Generate Robust SIV Immunity in Non-Human Primates.

Bhawna SharmaElena BekermanHoa TruongJohnny LeeMaria Gamez-GuerreroArchana BoopathyRohit MitalKatell Bidet HuangSarah Ahmadi-ErberRaphaela WimmerSophie SchulhaHenning LauterbachKlaus OrlingerSilpa SuthramMark G LewisWade BlairAzure Tariro MakadzangeRomas GeleziunasJeffrey P MurrySarah Schmidt
Published in: Vaccines (2024)
Arenavirus-based vectors are being investigated as therapeutic vaccine candidates with the potential to elicit robust CD8 T-cell responses. We compared the immunogenicity of replicating (artPICV and artLCMV) and non-replicating (rPICV and rLCMV) arenavirus-based vectors expressing simian immunodeficiency virus (SIV) Gag and Envelope (Env) immunogens in treatment-naïve non-human primates. Heterologous regimens with non-replicating and replicating vectors elicited more robust SIV IFN-γ responses than a homologous regimen, and replicating vectors elicited significantly higher cellular immunogenicity than non-replicating vectors. The heterologous regimen elicited high anti-Env antibody titers when administered intravenously, with replicating vectors inducing significantly higher titers than non-replicating vectors. Intramuscular immunization resulted in more durable antibody responses than intravenous immunization for both vector platforms, with no difference between the replicating and non-replicating vectors. Overall, both replicating and non-replicating arenavirus vectors generated robust T- and B-cell-mediated immunity to SIV antigens in treatment-naïve non-human primates, supporting further evaluation of these vectors in a clinical setting for HIV therapy.
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