Adjuvants influence the maturation of VRC01-like antibodies during immunization
Maria L. Knudsen,
Parul Agrawal,
Anna MacCamy,
K. Rachael Parks,
Matthew D. Gray,
Brittany N. Takushi,
Arineh Khechaduri,
Kelsey R. Salladay,
Rhea N. Coler,
Celia C. LaBranche,
David Montefiori,
Leonidas Stamatatos
Affiliations
Maria L. Knudsen
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Parul Agrawal
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Anna MacCamy
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
K. Rachael Parks
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA
Matthew D. Gray
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Brittany N. Takushi
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Arineh Khechaduri
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Kelsey R. Salladay
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Rhea N. Coler
Department of Global Health, University of Washington, Seattle, WA 98195, USA; Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, WA, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
Celia C. LaBranche
Division of Surgical Sciences, Duke University, Durham, NC 27710, USA
David Montefiori
Division of Surgical Sciences, Duke University, Durham, NC 27710, USA
Leonidas Stamatatos
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Corresponding author
Summary: Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether and how three adjuvants, Poly(I:C), GLA-LSQ, or Rehydragel, that activate different pathways of the innate immune system, influence the rate and type of somatic mutations accumulated by VRC01-class BCRs that become activated by the germline-targeting 426c.Mod.Core immunogen and the heterologous HxB2.WT.Core booster immunogen. We report that although the adjuvant used had no influence on the durability of plasma antibody responses after the prime, it influenced the plasma VRC01 antibody titers after the boost and the accumulation of somatic mutations on the elicited VRC01 antibodies.
