Escalating Dose Immunization Regimen in Non-Human Primates to Improve Immunogen-Specific Responses

Abstract

HIV-1 remains a major health threat, highlighting the need for a vaccine that induces broadly neutralizing antibodies. Epitope-based vaccine designs that focus humoral responses to vulnerable sites on the HIV-1 Env trimer protein are promising approaches, including those targeting the HIV-1 fusion peptide (FP). Escalating dose (ED) immunizations are a strategy to increase immunogen uptake into germinal centers and boost affinity maturation of the antiviral antibody response. In this study, we tested the impact of an ED immunization scheme on enhancing the FP-directed humoral response. Five groups of non-human primates were immunized: four received an ED immunization of either FP or a cocktail of FP+trimer, and one control group was dosed with a bolus FP+trimer cocktail. Two ED groups were adjuvanted with SMNP. The remaining groups used 3M052/alum. Fourteen weeks post-immunization, all ED groups had higher anti-FP IgG titers compared to the control, with the cocktail ED group adjuvanted with 3M052/alum characterized by 14.5-fold higher titers than the bolus control. While the ED cocktail and bolus groups had similar anti-trimer IgG titers, the ED groups had a higher non-base trimer response, shown by an 8.6-fold IgG increase between the 3M052/alum cocktail ED group and its bolus control. ED prime seems promising in raising anti-immunogen titers and lowering responses to the artificial trimer base, and further boosts will be administered to elicit serum neutralizing activity.