Posted in Meningococcal vaccines, Resource

Molecular signatures of antibody responses derived from a systems biological study of 5 human vaccines

Volcano plots comparing the differentially expressed genes after 3 days and 7 days post-vaccination with MCV4, MPSV4, YF-17D, TIV or LAIV vaccines. Source taken from Li et al., Nature Immunology, 2014.

Neisseria meningitidis is a leading cause of meningitis and septicemia with 1.2 million cases per year worldwide. Of note, bacterial polysaccharides do not trigger the same receptors that are involved in viral sensing. This brings an interesting question: Do carbohydrate vaccines induce the same or distinct molecular signatures as viral vaccines? To address this question, Shuzhao Li et al., 2014, compared the molecular signatures induced by meningococcal vaccines with yellow fever (YF-17D) and influenza vaccines (TIV and LAIV).

The two major classes of meningococcal vaccines tested are:

  1. The quadrivalent polysaccharide vaccine (MPSV4) containing polysaccharides from serogroups A, C, Y and W-135. Vaccine is given intramuscularly.
  2. The polysaccharide-protein conjugate vaccines, such as the quadrivalent conjugate vaccine (MCV4) that contains the same four polysaccharides conjugated to diphtheria toxoid. MCV4 given subcutaneously.

13 healthy subjects (age 18-45) received MPSV4 and 17 subjects received MCV4. Direct transcriptomic analysis on PBMCs was performed on days 0, 3 and 7 after vaccination.

The magnitude and duration of the polysaccharide-specific IgG response was greater with MPSV4 compared to a single dose of MCV4.

Peak levels of peripheral blood antibody secreting cells (ASCs) detected at day 7 post-vaccination.

Most DEGs for both vaccines were detected at day 7, with more DEGs in MCV4 vaccinees compared to MPSV4 vaccinees. Many of these DEGs were transcripts related to ASCs, which coincided with the increase in ASCs at day 7. XBP1 gene network was also enriched in MCV4 at day 7 post vaccination, similar to antibody signatures seen in subjects given the influenza inactivated vaccine. The signatures produced by MCV4 and MPSV4 were clearly distinct from the live-attenuated yellow fever and influenza vaccines.

Blood transcriptomic modules was used to decrypt immune responses produced by MCV and MPSV. Dendritic cell surface signature module, together with activation, complement and pro-inflammatory cytokines was correlated with anti-polysaccharide IgG in both MCV4 and MPSV4 vaccinees, suggesting the role of myeloid dendritic cells in antibody production. However, how these vaccines lead to myeloid dendritic cell activation still remains to be elucidated.

Data is deposited at Gene Expression Omnibus: GSE52245

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