Correlating IgG Levels with Neutralising Antibody Levels to Indicate Clinical Protection in Healthcare Workers at Risk during a Measles Outbreak

Abstract

The rapid transmission of measles poses a great challenge for measles elimination. Thus, rapid testing is required to screen the health status in the population during measles outbreaks. A pseudotype-based virus neutralisation assay was used to measure neutralising antibody titres in serum samples collected from healthcare workers in Sheffield during the measles outbreak in 2016. Vesicular stomatitis virus (VSV) pseudotypes bearing the haemagglutinin and fusion glycoproteins of measles virus (MeV) and carrying a luciferase marker gene were prepared; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity. Spearman’s correlation coefficients between IgG titres and neutralising antibody levels ranged from 0.40 to 0.55 (p < 0.05) or from 0.71 to 0.79 (p < 0.0001) when the IgG titres were obtained using different testing kits. In addition, the currently used vaccine was observed to cross-neutralise most circulating MeV genotypes. However, the percentage of individuals being “well-protected” was lower than 95%, the target rate of vaccination coverage to eliminate measles. These results demonstrate that the level of clinical protection against measles in individuals could be inferred by IgG titre, as long as a precise correlation has been established between IgG testing and neutralisation assay; moreover, maintaining a high vaccination coverage rate is still necessary for measles elimination.

Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases

“…Interestingly, not much difference in Nt-Ab titres was noted in Panel A between the two wild-type viruses (D4 and D8), however, Nt-Ab titres were about 50% lower for the MeV vaccine strain than for the wild-types, indicating either decay of immunity or likely non-responders amongst these one dose vaccine recipients. Similar observations in the neutralization pattern of different MeV vaccine and wild-type strains have been reported in Iran, the UK, Japan and the USA (11)(12)(13)(14). However, for the first time, cases where measles was suspected were subjected to detection of the MeV-specific IgM, IgG, IgG-avidity and Nt antibodies (vaccine/wild-types) and their suitability for helping to achieve the measles elimination goal in India was described.…”

“…A study from Iran revealed lower levels of Nt-Ab titres to MeV B3 genotype compared to the MeV genotypes A, D4 and H1 in individuals who were administered two doses of measles vaccine [11]. Sera from a group of healthcare workers from the UK showed that the titres for five circulating MeV genotypes (B3, C2, D4, D8 and H1) were significantly higher than the vaccine strain [12], whereas Japanese investigators demonstrated similar Nt-Ab titres for vaccine strain and circulating genotypes D3 and D5 strains in the serum samples obtained from the vaccine recipients [13]. Antigenic characterization of MeV wild-type (Chicago-1 strain, genotype D3) showed about five times higher titre compared to the vaccine strain [14].…”

The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

“…The median age of the participants was 30 years (IQR [26][27][28][29][30][31][32][33][34][35][36]. Most were female (69.8%), White (66.8%), healthcare workers (61.7%), and declared having no comorbidities (78.4%).…”

“…An American study aimed to validate commercial immunoassays and employed ELISA (Euroimmun ® ) and CLIA (LIAISON XL ® ) to evaluate measles antibodies titers compared to neutralization tests 27 . Both tests showed a positive correlation with neutralization, but ELISA demonstrated a stronger correlation (R=0.71-0.79; p<0.0001) than CLIA (R=0.40-0.55; p<0.05) and yielded more precise results.…”