Current perspectives in assessing humoral immunity after measles vaccination

Abstract

Introduction: Repeated measles outbreaks in countries with relatively high vaccine coverage are mainly due to failure to vaccinate and importation; however, cases in immunized individuals exist raising questions about suboptimal measles vaccine-induced humoral immunity and/or waning immunity in a low measles-exposure environment.

Areas covered: The plaque reduction neutralization measurement of functional measles-specific antibodies correlates with protection is the gold standard in measles serology, but it does not assess cellular-immune or other parameters that may be associated with durable and/or protective immunity after vaccination. Additional correlates of protection and long-term immunity and new determinants/signatures of vaccine responsiveness such as specific CD46 and IFI44L genetic variants associated with neutralizing antibody titers after measles vaccination are under investigation. Current and future systems biology studies, coupled with new technology/assays and analytical approaches, will lead to an increasingly sophisticated understanding of measles vaccine-induced humoral immunity and will identify 'signatures' of protective and durable immune responses.

Expert opinion: This will translate into the development of highly predictive assays of measles vaccine efficacy, effectiveness, and durability for prospective identification of potential low/non-responders and susceptible individuals who require additional vaccine doses. Such new advances may drive insights into the development of new/improved vaccine formulations and delivery systems.

Keywords: Measles; antibody; gene expression; gene polymorphisms; genetic association studies; genetic variation; humoral; immunity; measles vaccine; measles-mumps-rubella vaccine; systems biology.

Fig. 1

Measles virus receptor CD46 and functional effects of CD46 rs2724374 The figure above is published with permission from Human Genetics. [126, 127] The extracellular portion of CD46 consists of four N-glycosylated conserved short consensus repeats SCR1-4; a STP region that is O-glycosylated (encoded by exons 7/A, 8/B and 9/C); and a region of unknown function (U). The four most common CD46 isoforms are defined based on the present STP exon/exons and the cytoplasmic tail (CYT1 or CYT2): BC1 and BC2 (with B and C exons/domains in the STP and with either CYT1 or CYT2), and C1 and C2 (with C exon/domain in the STP and with either CYT1 or CYT2). The effect of CD46 rs2724374 on CD46 isoform prevalence (exon B expression or skipping), interaction between CD46 and MV, and immune response following measles vaccination is also summarized for the different genotypes.

Fig. 2

CyTOF and scRNA-Seq analysis of B cell subsets after vaccination. A) Schematic representation of CyTOF. t-SNE plot of cell clusters defined by cellular markers. The annotation of the numbered cell clusters is as follows: 1. naïve B cells; 2. memory B and 3. plasmablasts. For clarity only three of the relevant B cell clusters are shown. Heat map displaying the expression levels (blue=low, red=high) of each cell surface marker in columns and each B cell cluster of interest in rows. B) Schematic representation of scRNA-Seq. Heat map displaying the gene expression levels (green=low, red=high) within single B cells (assay cell input is purified B cells). Data integration allows for the identification of gene expression signatures within activated and/or antigen-specific B cell subsets after vaccination.