Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7 (4)

Genetic Variation in the Magnitude and Longevity of the IgG Subclass Response to a Diphtheria-Tetanus-Acellular Pertussis (DTaP) Vaccine in Mice

Affiliations

Genetic Variation in the Magnitude and Longevity of the IgG Subclass Response to a Diphtheria-Tetanus-Acellular Pertussis (DTaP) Vaccine in Mice

Yung-Yi C Mosley et al. Vaccines (Basel).

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.

Keywords: DTaP; IgG subclass; antibody longevity; antibody magnitude; genetics; vaccine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
IgG1, IgG2b, and IgG3 titers to Diphtheria-Tetanus-Acellular Pertussis (DTaP) vaccine antigens in inbred mouse strains. Titers were determined at week 14 (two weeks after the third vaccination) against four antigens in the DTaP vaccine by ELISA. There was significant variation (p < 0.0001 by ANOVA) between the antibody magnitude from 28 strains of mice for diphtheria toxoid (DT), pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (Prn) for each IgG subclass.
Figure 2
Figure 2
Correlations between IgG1, IgG2b, and IgG3 against the same vaccine antigen. The correlations between IgG1, IgG2b, and IgG3 were plotted against the same vaccine antigen for antibody magnitude (a) and longevity (b). Mean value of the longevity of each strain was used to calculate for Pearson’s correlation coefficient (r) for the correlations between the magnitude and longevity of IgG1 and IgG2b, IgG1 and IgG3, IgG2b and IgG3. Significant values (p < 0.05) are indicated in red font.
Figure 3
Figure 3
Correlations between antigen-specific responses among IgG1, IgG2b, and IgG3. The correlations between antibody response to different vaccine antigens for IgG1, IgG2b, and IgG3 were plotted for antibody magnitude (a) and longevity (b). The correlations were presented by Pearson r values for each pair of antigen-specific antibody within the same IgG subclass. Significant values (p < 0.05) are indicated in red font.
Figure 4
Figure 4
IgG1/IgG3 ratios for different vaccine antigens. (a) IgG1 to IgG3 ratios were calculated as log(IgG1/IgG3) for titers measured at wk14 of age. The calculated Pearson correlation coefficients of IgG1/IgG3 ratio (average value of each strain) between the four DTaP antigens were all significant as indicated by the p-values. (b) Number of genes identified by genome-wide association mapping algorithm for IgG1/IgG3 ratio were plotted by Venn diagram.
Figure 5
Figure 5
Ranking of mouse strains based on the mean of the IgG1/IgG3 ratios of the four vaccine antigens. A low IgG1/IgG3 ratio indicates Th1-prone and a high ratio indicates Th2-prone. NA: Antibodies induced against Prn in PWK/PhJ mice were below the cutoff and this was eliminated from the analysis.
Figure 6
Figure 6
Effect of TLR4 on the magnitude antigen-specific IgG subclass titers in mice immunized with DTaP. Antibody titers at wk14 of age were compared between C3H/HeJ (TLR4-deficient) and C3H/HeOuJ (TRL4-sufficient) mice. * p < 0.05; ** p < 0.01; *** p < 0.005.

Similar articles

See all similar articles

References

    1. Vidarsson G., Dekkers G., Rispens T. IgG subclasses and allotypes: From structure to effector functions. Front. Immunol. 2014;5:520. doi: 10.3389/fimmu.2014.00520. - DOI - PMC - PubMed
    1. Jouvin-Marche E., Morgado M.G., Leguern C., Voegtle D., Bonhomme F., Cazenave P.A. The mouse Igh-1a and Igh-1b H chain constant regions are derived from two distinct isotypic genes. Immunogenetics. 1989;29:92–97. doi: 10.1007/BF00395856. - DOI - PubMed
    1. Morgado M.G., Cam P., Gris-Liebe C., Cazenave P.A., Jouvin-Marche E. Further evidence that BALB/c and C57BL/6 gamma 2a genes originate from two distinct isotypes. EMBO J. 1989;8:3245–3251. doi: 10.1002/j.1460-2075.1989.tb08484.x. - DOI - PMC - PubMed
    1. Zhang Z., Goldschmidt T., Salter H. Possible allelic structure of IgG2a and IgG2c in mice. Mol. Immunol. 2012;50:169–171. doi: 10.1016/j.molimm.2011.11.006. - DOI - PubMed
    1. Martin R.M., Silva A., Lew A.M. The Igh-1 sequence of the non-obese diabetic (NOD) mouse assigns it to the IgG2c isotype. Immunogenetics. 1997;46:167–168. doi: 10.1007/s002510050258. - DOI - PubMed
Feedback