title: Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses.
abstract: Antibodies raised in Indian rhesus macaques [Macaca mulatta(MM)] in many preclinical vaccine studies are often evaluatedin vitrofor titer, antigen-recognition breadth, neutralization potency, and/or effector function, andin vivofor potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical,in vitro, andin vivocharacterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies.
authors.affiliation: Thayer School of Engineering, Dartmouth College , Hanover, NH , USA.
authors.forename: Austin W
authors.initials: AW
authors.lastname: Boesch
authors.affiliation: Molecular and Cellular Biology Program, Dartmouth College , Hanover, NH , USA.
authors.forename: Nana Yaw
authors.initials: NY
authors.lastname: Osei-Owusu
authors.affiliation: Molecular and Cellular Biology Program, Dartmouth College , Hanover, NH , USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Crowley
authors.affiliation: Thayer School of Engineering, Dartmouth College , Hanover, NH , USA.
authors.forename: Thach H
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Thayer School of Engineering, Dartmouth College , Hanover, NH , USA.
authors.forename: Ying N
authors.initials: YN
authors.lastname: Chan
authors.affiliation: Thayer School of Engineering, Dartmouth College , Hanover, NH , USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Weiner
authors.affiliation: Molecular and Cellular Biology Program, Dartmouth College , Hanover, NH , USA.
authors.forename: Pranay
authors.initials: P
authors.lastname: Bharadwaj
authors.affiliation: Molecular and Cellular Biology Program, Dartmouth College, Hanover, NH, USA; Department of Genetics and Biochemistry, Geisel School of Medicine, Hanover, NH, USA.
authors.forename: Rufus
authors.initials: R
authors.lastname: Hards
authors.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine , Lebanon, NH , USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Adamo
authors.affiliation: Molecular and Cellular Biology Program, Dartmouth College, Hanover, NH, USA; Department of Genetics and Biochemistry, Geisel School of Medicine, Hanover, NH, USA; Norris Cotton Cancer Center, Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Cocklin
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA , USA.
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Wasatch Microfluidics , Salt Lake City, UT , USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Miles
authors.affiliation: Wasatch Microfluidics , Salt Lake City, UT , USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Eckman
authors.affiliation: Non-Human Primate Reagent Resource, MassBiologics of the University of Massachusetts Medical School , Boston, MA , USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Belli
authors.affiliation: Non-Human Primate Reagent Resource, MassBiologics of the University of Massachusetts Medical School , Boston, MA , USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA; Molecular and Cellular Biology Program, Dartmouth College, Hanover, NH, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
keywords: Fc receptor; IgG; effector function; non-human primate; rhesus