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Abstract
The type of IgG subclasses induced by vaccination is an important determinant of vaccine efficacy because the IgG subclasses vary in their biological function. The goal of this study was to determine the influence of the genetic background on the production and duration of vaccine-induced IgG subclasses. IgG1, IgG2b, and IgG3 titers against diphtheria toxoid (DT), pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn) were measured in mice from 28 different inbred and wild-derived strains vaccinated with an aluminum hydroxide-adjuvanted DTaP vaccine. The titers and duration of vaccine-specific IgG subclass responses were different among mouse strains, indicating that genetic factors contribute to this variation. Statistical associations were used to identify potential mechanisms that contribute to antibody production and longevity. This analysis showed that the mechanisms guiding the magnitude of antibody production were antigen-dependent for IgG1 but antigen-independent for IgG2b and IgG3. However, the mechanisms driving the longevity of antibody titers were antigen-independent for IgG1, IgG2b, and IgG3. The ratio of IgG1 and IgG3 titers identified Th1 and Th2-prone mouse strains. TLR4-deficient C3H/HeJ mice had an enhanced IgG1 response compared with C3H/HeOuJ mice with intact TLR4. This work demonstrates that the genetic background contributes significantly to the magnitude and longevity of vaccine-induced IgG1, IgG2b, and IgG3 titers in mice.
Highlights
IntroductionHuman and mouse immunoglobulins are classified into five isotypes, i.e., IgA, IgD, IgE, IgG, and IgM, which differ in their heavy chain structure and corresponding effector function [1]
Human and mouse immunoglobulins are classified into five isotypes, i.e., IgA, IgD, IgE, IgG, and IgM, which differ in their heavy chain structure and corresponding effector function [1].In mice, IgG is further divided into IgG1, IgG2a, IgG2b, IgG2c, and IgG3 subclasses
The diphtheria-tetanus-acellular pertussis (DTaP) vaccine used in this study contains five antigens formulated with aluminum hydroxide adjuvant
Summary
Human and mouse immunoglobulins are classified into five isotypes, i.e., IgA, IgD, IgE, IgG, and IgM, which differ in their heavy chain structure and corresponding effector function [1]. IgG is further divided into IgG1, IgG2a, IgG2b, IgG2c, and IgG3 subclasses. Except for IgG2a and IgG2c, IgG subclasses are shared among inbred mouse strains. Inbred mice either have an Igh-1a or Igh-1b allele at their heavy chain locus which encodes for IgG2a and. IgG2c, respectively [2,3,4]. BALB/cJ and C3H/HeJ mice express IgG2a, whereas. C57BL/6J and NOD/ShiLtJ mice have IgG2c [3,5].
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