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Application of a fast and cost-effective ‘three-in-one’ MMR ELISA as a tool for surveying anti-MMR humoral immunity: the Hungarian experience

  • K. Böröcz (a1), Z. Csizmadia (a1), Á. Markovics (a2), N. Farkas (a3), J. Najbauer (a1), T. Berki (a1) and P. Németh (a1)...

Abstract

In Hungary, between February 2017 and July 2019, 70 confirmed measles cases were reported, raising questions about the adequacy of population-level immunity. Although the assumed vaccination coverage is ≥99%, in a recent study, we detected potential gaps in the anti-measles humoral immunity. In Hungary, according to a decree by the Ministry of Public Welfare, beginning from 2021, the healthcare provider should conduct a serosurvey of anti-measles protection levels of healthcare professionals. To facilitate the compliance with this requirement, we developed a quick ‘three-in-one’ or ‘triple’ MMR (measles, mumps and rubella) indirect ELISA (IgG); an assay format that is currently not available commercially. High throughput applicability of the ‘three-in-one’ ELISA was verified using 1736 sera from routine laboratory residual samples, using an automated platform (Siemens BEP 2000 Advance). Assay verification was performed by comparing the full antigen repertoire-based ‘target’ assay with in-house ‘control’ assays using recombinant viral antigen coatings, and by validated commercially available kits. Indirect immunofluorescence was used as an independent reference method. Data were analysed using OriginLab, IBM SPSS, RStudio and MedCalc. In case of measles, we combined our current results with previously published data (Ntotal measles = 3523). Evaluation of anti-mumps and anti-rubella humoral antibody levels was based on the measurement of 1736 samples. The lowest anti-measles seropositivity (79.3%) was detected in sera of individuals vaccinated between 1978 and 1987. Considering the antigen-specific seropositivity ratios of all samples measured, anti-measles, -mumps and -rubella IgG antibody titres were adequate in 89.84%, 91.82% and 92.28%, respectively. Based on the virus-specific herd immunity threshold (HIT) values (HITMeasles = 92–95%, HITMumps = 75–86%, HITRubella = 83–86), it can be stated that regarding anti-measles immunity, certain age clusters of the population may have inadequate levels of humoral immunity. Despite the potential gaps in herd immunity, the use of MMR vaccine remains an effective and low-cost approach for the prevention of measles, mumps and rubella infections.

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Copyright

Published by Cambridge Universty Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Author for correspondence: Katalin Böröcz, E-mail: borocz.katalin@pte.hu

References

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1.Haralambieva, IH et al. (2015) Variability in humoral immunity to measles vaccine: new developments. Trends in Molecular Medicine 21, 789801.
2.Tabacchi, G et al. (2016) Determinants of European parents’ decision on the vaccination of their children against measles, mumps and rubella: a systematic review and meta-analysis. Vaccines & Immunotherapeutics 12, 19091923.
3.European Centre for Disease Control (2019) Insufficient vaccination coverage in EU/EEA fuels continued measles circulation. Available at https://ecdc.europa.eu/en/news-events/ecdc-insufficient-vaccination-coverage-eueea-fuels-continued-measles-circulation. Accessed 24 July 2019.
4.Zimmerman, LA et al. (2019) Progress toward measles elimination – European region, 2009–2018. MMWR. Morbidity and Mortality Weekly Report Centers for Disease Control and Prevention 68, 396401.
5.Centers for Disease Control and Prevention (1989) International Notes Measles – Hungary. MMWR Weekly 38, 665668. Available at https://www.cdc.gov/mmwr/preview/mmwrhtml/00001472.htm
6.World Health Organization (2019) New measles surveillance data from WHO. World Health Organization. Published online: 2019. Available at https://www.who.int/news-room/fact-sheets/detail/measles
7.Wadman, M (2019) Measles epidemic in Ukraine drove troubling European year. Science 363, 677678.
8.The Lancet Editorial (2018) Measles, war, and health-care reforms in Ukraine. The Lancet 392, 711. doi: 10.1016/S0140-6736(18)31984-6.
9.World Health Organization (2018) A report on the epidemiology of selected vaccine-preventable diseases in the European Region. WHO EpiBrief No. 1/2018.
10.Angelo, KM et al. (2019) Spread of Measles in Europe and Implications for US Travelers. Pediatrics 144, e20190414. doi: 10.1542/peds.2019-0414.
11.Molnár, Z et al. (2007) Local mumps outbreak in Hungary, 2007. Weekly Releases (1997–2007) European Centre for Disease Prevention and Control 12, 3167.
12.World Health Organization (2017) Measles and rubella elimination country profile Hungary. Available at http://www.euro.who.int/__data/assets/pdf_file/0013/401116/HUN.pdf?ua=1
13.European Centre for Disease Control (2019). Monthly measles and rubella monitoring report, April 2019.
14.World Health Organization (2018). Hungary: WHO and UNICEF estimates of immunization coverage: 2018 revision.
15.Lambert, N et al. (2015) Rubella. The Lancet 385, 22972307.
16.Moss, WJ (2017) Measles. The Lancet 390, 24902502.
17.Lewnard, JA and Grad, YH (2018) Vaccine waning and mumps re-emergence in the United States. Science Translational Medicine 10, eaao5945.
18.Hviid, A, Rubin, S and Mühlemann, K (2008) Mumps. The Lancet 371, 932944.
19.MMWR Weekly. MMWR publications | MMWR. Available at https://www.cdc.gov/mmwr/publications/index.html
20.Liu, Y et al. (2018) Waning immunity of one-dose measles-mumps-rubella vaccine to mumps in children from kindergarten to early school age: a prospective study. Expert Review of Vaccines 17, 445452.
21.Bankamp, B et al. (2019) Successes and challenges for preventing measles, mumps and rubella by vaccination. Current Opinion in Virology 34, 110116.
22.Kontio, M et al. (2012) Waning antibody levels and avidity: implications for MMR vaccine-induced protection. Journal of Infectious Diseases 206, 15421548.
23.Gibney, KB et al. (2019) Emergence of attenuated measles illness among IgG positive/IgM negative measles cases, Victoria, Australia 2008–2017. Clinical Infectious Diseases. Published online: 6 May 2019. doi: 10.1093/cid/ciz363.
24.Böröcz, K et al. (2019) Development of a robust and standardized immunoserological assay for detection of anti-measles IgG antibodies in human sera. Journal of Immunological Methods 464, 18.
25.Griner, PF, Mayewski, RJ and Mushlin, AIGP (1981) Selection and interpretation of diagnostic tests and procedures. Principles and applications. – PubMed – NCBI. Annals of Internal Medicine 94, 557592.
26.European Centre for Disease Control (2018) Surveillance Report Annual Epidemiological Report for 2016 Mumps. Available at https://www.ecdc.europa.eu/sites/default/files/documents/AER_for_2016-mumps-rev.pdf
27.Redd, SC et al. (2004) Comparison of vaccination with measles-mumps-rubella vaccine at 9, 12, and 15 months of age. Hinman AR, ed. The Journal of Infectious Diseases 189, S116S122.
28.Orenstein, WA et al. (1986) Appropriate age for measles vaccination in the United States. Developments in Biological Standardization 65, 1321.
29.World Health Organization (2009) The Immunological Basis for Immunization Series. Module 7: Measles Update 2009.
30.Health Service Executive, Ireland (2019) Chapter 3 Immunisation of Immunocompromised Persons. Available at https://www.hse.ie/eng/health/immunisation/hcpinfo/guidelines/chapter3.pdf
31.Arvas, A (2014) Vaccination in patients with immunosuppression. Turk pediatri arsivi 49, 181185.
32.Lengyel, G et al. (2019) Screening of more than 2000 Hungarian healthcare workers’ anti-measles antibody level: results and possible population-level consequences. Epidemiology and Infection 147, e7.
33.Agócs, MM et al. (1992) The 1988–1989 measles epidemic in Hungary: assessment of vaccine failure. International Journal of Epidemiology 21, 10071013.
34.Fine, P, Eames, K and Heymann, DL (2011) ‘Herd immunity’: a rough guide. Clinical Infectious Diseases 52, 911916.
35.Edmunds, WJ et al. (2000) The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies. Epidemiology and Infection 125, 635650.
36.Guerra, FM et al. (2017) The basic reproduction number (R0) of measles: a systematic review. The Lancet. Infectious Diseases 17, e420e428.
37.Masterson, SG et al. (2018) Herd immunity to ebolaviruses is not a realistic target for current vaccination strategies. Frontiers in Immunology 9, 1025.
38.World Health Organization (2018) Manual for the Laboratory-based Surveillance of Measles, Rubella, and Congenital Rubella Syndrome. Third edition, June 2018.
39.Vyse, AJ et al. (2006) Interpreting serological surveys using mixture models: the seroepidemiology of measles, mumps and rubella in England and wales at the beginning of the 21st century. Epidemiology and Infection 134, 13031312.
40.Skendzel, LP (1996) Rubella immunity: defining the level of protective antibody. American Journal of Clinical Pathology 106, 170174.
41.Ward, BJ et al. (1995) Cellular immunity in measles vaccine failure: demonstration of measles antigen-specific lymphoproliferative responses despite limited serum antibody production after revaccination. Journal of Infectious Diseases 172, 15911595.
42.Plotkin, SA (2010) Correlates of protection induced by vaccination. Clinical and Vaccine Immunology: CVI 17, 10551065.
43.Plotkin, SA and Gilbert, PB (2012) Nomenclature for immune correlates of protection after vaccination. Clinical Infectious Diseases 54, 16151617.
44.World Health Organization (2013) Correlates of vaccine-induced protection: methods and implications. WHO reference number: WHO/IVB/13.01.
45.Dorigo-Zetsma, JW et al. (2015) Immune status of health care workers to measles virus: evaluation of protective titers in four measles IgG EIAs. Journal of Clinical Virology 69, 214218.
46.Tischer, A et al. (2007) Vaccinated students with negative enzyme immunoassay results show positive measles virus-specific antibody levels by immunofluorescence and plaque neutralisation tests. Journal of Clinical Virology 38, 204209.

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Application of a fast and cost-effective ‘three-in-one’ MMR ELISA as a tool for surveying anti-MMR humoral immunity: the Hungarian experience

  • K. Böröcz (a1), Z. Csizmadia (a1), Á. Markovics (a2), N. Farkas (a3), J. Najbauer (a1), T. Berki (a1) and P. Németh (a1)...

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