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A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines.

Vestrheim AC, Moen A, Egge-Jacobsen W, Reubsaet L, Halvorsen TG, Bratlie DB, Paulsen BS, Michaelsen TE - Immun Inflamm Dis (2014)

Bottom Line: The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect.The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine.This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology & Immunology, Norwegian Institute of Public Health Oslo, Norway ; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo Oslo, Norway.

ABSTRACT
The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect. Detailed structural carbohydrate analysis of vaccine induced IgGs is therefore of interest as this knowledge can prove valuable in vaccine research and design and when optimizing vaccine schedules. In order to better understand and exploit the protective potential of IgG antibodies, we carried out a pilot study; collecting serum or plasma from volunteers receiving different vaccines and determining the IgG subclass glycosylation patterns against specific vaccine antigens at different time points using LC-ESI-MS analysis. The four vaccines included a pneumococcal capsule polysaccharide vaccine, a meningococcal outer membrane vesicle vaccine, a seasonal influenza vaccine, and a pandemic influenza vaccine. The number of volunteers was limited, but the results following immunization indicated that the IgG subclass which dominated the response showed increased galactose and the level of sialic acid increased with time for most vaccinees. Fucose levels increased for some vaccinees but in general stayed relatively unaltered. The total background IgG glycosylation analyzed in parallel varied little with time and hence the changes seen were likely to be caused by vaccination. The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine. This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.

No MeSH data available.


Related in: MedlinePlus

The three main time points for all four vaccines presented as percentage distribution of galactosylation, fucosylation, sialylation and bisecting GlcNAc. Pneumococcal IgG2 is displayed by A, B, C, and D while pandemic influenza IgG1 is presented as E, F, G, and H. I, J, K, and L show seasonal influenza IgG1 and M, N, O, and P show meningococcal IgG1. The time points for the meningococcal vaccine were visit 4 (1–2 weeks after third dose), visit 6 (10–12 months after third dose), and visit 7 (1–2 weeks after fourth dose). Two of the vaccinees that received the pneumococcal vaccine had their second and third sample collected at day 14 and day 26, not day 30 and day 90 as the others. The results were however similar to the others at day 30 and day 90, so to ease presentation their time points were presented as day 30 and 90, thus showing trend similarities. The y-axis portrays percentage distribution of glycoforms. See Table1 for full details of the meningococcal vaccine schedule.
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fig04: The three main time points for all four vaccines presented as percentage distribution of galactosylation, fucosylation, sialylation and bisecting GlcNAc. Pneumococcal IgG2 is displayed by A, B, C, and D while pandemic influenza IgG1 is presented as E, F, G, and H. I, J, K, and L show seasonal influenza IgG1 and M, N, O, and P show meningococcal IgG1. The time points for the meningococcal vaccine were visit 4 (1–2 weeks after third dose), visit 6 (10–12 months after third dose), and visit 7 (1–2 weeks after fourth dose). Two of the vaccinees that received the pneumococcal vaccine had their second and third sample collected at day 14 and day 26, not day 30 and day 90 as the others. The results were however similar to the others at day 30 and day 90, so to ease presentation their time points were presented as day 30 and 90, thus showing trend similarities. The y-axis portrays percentage distribution of glycoforms. See Table1 for full details of the meningococcal vaccine schedule.

Mentions: All vaccines induced increased galactosylation from day 0 to day 30 after vaccination (see Fig. 4A, E, I, and M). From day 30 to day 90, galactose levels varied between different vaccines and for individual vaccinees; no change or a slight decrease for pneumococcal IgG2 while pandemic IgG1 either increased or decreased. For the extra pandemic influenza samples, an increase was seen at day 290 (vaccinee # 005) and day 559 (vaccinee # 006), both from the younger volunteers, while for one 65+ volunteer, a decrease was seen at day 201. Galactose levels in seasonal influenza IgG1 stayed stabile or decreased from day 30 to day 90, while meningococcal IgG1 increased after vaccination (visit 7) and showed inconsistent patterns between vaccinees after time.


A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines.

Vestrheim AC, Moen A, Egge-Jacobsen W, Reubsaet L, Halvorsen TG, Bratlie DB, Paulsen BS, Michaelsen TE - Immun Inflamm Dis (2014)

The three main time points for all four vaccines presented as percentage distribution of galactosylation, fucosylation, sialylation and bisecting GlcNAc. Pneumococcal IgG2 is displayed by A, B, C, and D while pandemic influenza IgG1 is presented as E, F, G, and H. I, J, K, and L show seasonal influenza IgG1 and M, N, O, and P show meningococcal IgG1. The time points for the meningococcal vaccine were visit 4 (1–2 weeks after third dose), visit 6 (10–12 months after third dose), and visit 7 (1–2 weeks after fourth dose). Two of the vaccinees that received the pneumococcal vaccine had their second and third sample collected at day 14 and day 26, not day 30 and day 90 as the others. The results were however similar to the others at day 30 and day 90, so to ease presentation their time points were presented as day 30 and 90, thus showing trend similarities. The y-axis portrays percentage distribution of glycoforms. See Table1 for full details of the meningococcal vaccine schedule.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4217548&req=5

fig04: The three main time points for all four vaccines presented as percentage distribution of galactosylation, fucosylation, sialylation and bisecting GlcNAc. Pneumococcal IgG2 is displayed by A, B, C, and D while pandemic influenza IgG1 is presented as E, F, G, and H. I, J, K, and L show seasonal influenza IgG1 and M, N, O, and P show meningococcal IgG1. The time points for the meningococcal vaccine were visit 4 (1–2 weeks after third dose), visit 6 (10–12 months after third dose), and visit 7 (1–2 weeks after fourth dose). Two of the vaccinees that received the pneumococcal vaccine had their second and third sample collected at day 14 and day 26, not day 30 and day 90 as the others. The results were however similar to the others at day 30 and day 90, so to ease presentation their time points were presented as day 30 and 90, thus showing trend similarities. The y-axis portrays percentage distribution of glycoforms. See Table1 for full details of the meningococcal vaccine schedule.
Mentions: All vaccines induced increased galactosylation from day 0 to day 30 after vaccination (see Fig. 4A, E, I, and M). From day 30 to day 90, galactose levels varied between different vaccines and for individual vaccinees; no change or a slight decrease for pneumococcal IgG2 while pandemic IgG1 either increased or decreased. For the extra pandemic influenza samples, an increase was seen at day 290 (vaccinee # 005) and day 559 (vaccinee # 006), both from the younger volunteers, while for one 65+ volunteer, a decrease was seen at day 201. Galactose levels in seasonal influenza IgG1 stayed stabile or decreased from day 30 to day 90, while meningococcal IgG1 increased after vaccination (visit 7) and showed inconsistent patterns between vaccinees after time.

Bottom Line: The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect.The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine.This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology & Immunology, Norwegian Institute of Public Health Oslo, Norway ; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo Oslo, Norway.

ABSTRACT
The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect. Detailed structural carbohydrate analysis of vaccine induced IgGs is therefore of interest as this knowledge can prove valuable in vaccine research and design and when optimizing vaccine schedules. In order to better understand and exploit the protective potential of IgG antibodies, we carried out a pilot study; collecting serum or plasma from volunteers receiving different vaccines and determining the IgG subclass glycosylation patterns against specific vaccine antigens at different time points using LC-ESI-MS analysis. The four vaccines included a pneumococcal capsule polysaccharide vaccine, a meningococcal outer membrane vesicle vaccine, a seasonal influenza vaccine, and a pandemic influenza vaccine. The number of volunteers was limited, but the results following immunization indicated that the IgG subclass which dominated the response showed increased galactose and the level of sialic acid increased with time for most vaccinees. Fucose levels increased for some vaccinees but in general stayed relatively unaltered. The total background IgG glycosylation analyzed in parallel varied little with time and hence the changes seen were likely to be caused by vaccination. The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine. This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.

No MeSH data available.


Related in: MedlinePlus