Unravelling the Measles Paradox (MISIA)

NCT07267585 | Recruiting

• 1 other identifier: NL-005630
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The measles (MeV) paradox refers to an apparent contradiction: natural measles causes a transient but profound immune suppression putting patients at risk for opportunistic infections for years, while at the same time MeV infection induces robust immune activation leading to lifelong protection against measles. In this protocol, we test our hypothesis that natural measles causes immune amnesia by altering the composition of circulating immune memory cells. In comparison to the prior studies performed during the 2013 outbreak, we will specifically determine \[1\] to what extent pre-existing immunity is reduced, \[2\] for how long this functional immune suppression can be detected, and \[3\] to what extent MeV-specific immune cells expand. Recently, the WHO reported a 30-fold increase of the number of measles cases in the European Region in 2023 and the ECDC has published a threat assessment brief on increase of the number of cases and considerations for public health response. Combined with the reported drop in vaccination coverage, and several clusters of cases, we anticipate that we are at the verge of a new measles outbreak in the Netherlands

Conditions

MEASLES DISEASE

Outcome Measures

Primary Outcomes (2)

• Compare measles-induced loss of pathogen-specific antibodies

  The investigators will measure changes in the immune repertoire using longitudinal samples obtained from participants who are infected with MeV. To this end, they will measure pathogen-specific antibody responses (titers) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific antibodies.

  36 months

• Compare measles-induced loss of pathogen-specific T-cells

  The investigators will measure changes in the immune repertoire using longitudinal samples obtained from participants who are infected with MeV. To this end, they will measure pathogen-specific T-cell responses (frequencies) pre- and post-measles and compare these to determine whether measles led to a loss of pathogen-specific T-cells.

  36 months

Study Arms (5)

Group A (receive measles vaccine in 2024)

Participant who never had measles vaccine and are recently vaccinated against measles before the upcoming outbreak.

Group B (not vaccinated, measles infection during upcoming outbreak)

Participants who never had measles vaccine and decline recent offer for measles vaccine and get infected with measles during the upcoming outbreak.

Group C (not vaccinated, no measles infection during upcoming outbreak)

Participants who never had measles vaccine and decline recent offer for measles vaccine and remain free from measles infection.

Group D (not vaccinated, historical infection)

Participants who never had measles vaccine and had a history of measles infection.

Group E (historically vaccinated)

Participants who have received measles vaccine about 10 years ago.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The participants in this study are 18 years or older and will be recruited in areas with low vaccination coverage. Recruitment will occur through contacting orthodox protestant student associations, GPs with a large orthodox protestant patient base, orthodox protestant newspapers, and first year medical students at the Erasmus MC. The study does not include an intervention.

You may qualify if:

• Cohort A
• years or older
• No known history of measles or vaccination
• Decided to take MMR vaccination before the upcoming measles outbreak
• Cohort B
• years or older
• No known history of measles or vaccination (seronegative confirmed)
• Contracted measles during the upcoming outbreak
• Cohort C
• years or older
• No known history of measles or vaccination (seronegative confirmed)
• Cohort D
• years or older
• Experienced measles during the 2013 outbreak
• Cohort E

You may not qualify if:

• A potential participant who meets any of the following criteria will be excluded from the study:
• Diagnosed chronic disease
• Immune suppression (due to medication or underlying disease)
• Additionally for subjects recruited to Cohort A:
• pregnant women or women planning to get pregnant in less than one month after the start of the study. This is a precaution; the MMR vaccine is not recommended for pregnant women.
• People who have had a severe allergic reaction (e.g., anaphylaxis) after a previous vaccination.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus MC

Rotterdam, South Holland, 3015GD, Netherlands

RECRUITING

Related Publications (25)

• Knol M, Urbanus A, Swart E, Mollema L, Ruijs W, van Binnendijk R, Te Wierik M, de Melker H, Timen A, Hahne S. Large ongoing measles outbreak in a religious community in the Netherlands since May 2013. Euro Surveill. 2013 Sep 5;18(36):pii=20580. doi: 10.2807/1560-7917.es2013.18.36.20580.

  PMID: 24079377 BACKGROUND

• Van Den Hof S, Smit C, Van Steenbergen JE, De Melker HE. Hospitalizations during a measles epidemic in the Netherlands, 1999 to 2000. Pediatr Infect Dis J. 2002 Dec;21(12):1146-50. doi: 10.1097/00006454-200212000-00012.

  PMID: 12488666 BACKGROUND

• van Velzen E, de Coster E, van Binnendijk R, Hahne S. Measles outbreak in an anthroposophic community in The Hague, The Netherlands, June-July 2008. Euro Surveill. 2008 Jul 31;13(31):18945. No abstract available.

  PMID: 18761905 BACKGROUND

• Mollema L, Harmsen IA, Broekhuizen E, Clijnk R, De Melker H, Paulussen T, Kok G, Ruiter R, Das E. Disease detection or public opinion reflection? Content analysis of tweets, other social media, and online newspapers during the measles outbreak in The Netherlands in 2013. J Med Internet Res. 2015 May 26;17(5):e128. doi: 10.2196/jmir.3863.

  PMID: 26013683 BACKGROUND

• Laksono BM, de Vries RD, Verburgh RJ, Visser EG, de Jong A, Fraaij PLA, Ruijs WLM, Nieuwenhuijse DF, van den Ham HJ, Koopmans MPG, van Zelm MC, Osterhaus ADME, de Swart RL. Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands. Nat Commun. 2018 Nov 23;9(1):4944. doi: 10.1038/s41467-018-07515-0.

  PMID: 30470742 BACKGROUND

• Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljander H, Rewers M, Choy DF, Wilson MS, Larman HB, Nelson AN, Griffin DE, de Swart RL, Elledge SJ. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019 Nov 1;366(6465):599-606. doi: 10.1126/science.aay6485.

  PMID: 31672891 BACKGROUND

• Rennick LJ, de Vries RD, Carsillo TJ, Lemon K, van Amerongen G, Ludlow M, Nguyen DT, Yuksel S, Verburgh RJ, Haddock P, McQuaid S, Duprex WP, de Swart RL. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates. J Virol. 2015 Feb;89(4):2192-200. doi: 10.1128/JVI.02924-14. Epub 2014 Dec 3.

  PMID: 25473055 BACKGROUND

• de Vries RD, Lemon K, Ludlow M, McQuaid S, Yuksel S, van Amerongen G, Rennick LJ, Rima BK, Osterhaus AD, de Swart RL, Duprex WP. In vivo tropism of attenuated and pathogenic measles virus expressing green fluorescent protein in macaques. J Virol. 2010 May;84(9):4714-24. doi: 10.1128/JVI.02633-09. Epub 2010 Feb 24.

  PMID: 20181691 BACKGROUND

• Aaby P, Bukh J, Lisse IM, Smits AJ. Measles vaccination and reduction in child mortality: a community study from Guinea-Bissau. J Infect. 1984 Jan;8(1):13-21. doi: 10.1016/s0163-4453(84)93192-x.

  PMID: 6699411 BACKGROUND

• Sato R, Haraguchi M. Effect of measles prevalence and vaccination coverage on other disease burden: evidence of measles immune amnesia in 46 African countries. Hum Vaccin Immunother. 2021 Dec 2;17(12):5361-5366. doi: 10.1080/21645515.2021.2013078. Epub 2021 Dec 29.

  PMID: 34965183 BACKGROUND

• Petrova VN, Sawatsky B, Han AX, Laksono BM, Walz L, Parker E, Pieper K, Anderson CA, de Vries RD, Lanzavecchia A, Kellam P, von Messling V, de Swart RL, Russell CA. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019 Nov 1;4(41):eaay6125. doi: 10.1126/sciimmunol.aay6125.

  PMID: 31672862 BACKGROUND

• Cox RM, Wolf JD, Lieberman NA, Lieber CM, Kang HJ, Sticher ZM, Yoon JJ, Andrews MK, Govindarajan M, Krueger RE, Sobolik EB, Natchus MG, Gewirtz AT, deSwart RL, Kolykhalov AA, Hekmatyar K, Sakamoto K, Greninger AL, Plemper RK. Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets. Nat Commun. 2024 Feb 8;15(1):1189. doi: 10.1038/s41467-024-45418-5.

  PMID: 38331906 BACKGROUND

• Laksono BM, Roelofs D, Comvalius AD, Schmitz KS, Rijsbergen LC, Geers D, Nambulli S, van Run P, Duprex WP, van den Brand JMA, de Vries RD, de Swart RL. Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease. mSphere. 2023 Aug 24;8(4):e0008223. doi: 10.1128/msphere.00082-23. Epub 2023 Jun 28.

  PMID: 37377421 BACKGROUND

• Ward BJ, Johnson RT, Vaisberg A, Jauregui E, Griffin DE. Cytokine production in vitro and the lymphoproliferative defect of natural measles virus infection. Clin Immunol Immunopathol. 1991 Nov;61(2 Pt 1):236-48. doi: 10.1016/s0090-1229(05)80027-3.

  PMID: 1914259 BACKGROUND

• Hirsch RL, Griffin DE, Johnson RT, Cooper SJ, Lindo de Soriano I, Roedenbeck S, Vaisberg A. Cellular immune responses during complicated and uncomplicated measles virus infections of man. Clin Immunol Immunopathol. 1984 Apr;31(1):1-12. doi: 10.1016/0090-1229(84)90184-3.

  PMID: 6230187 BACKGROUND

• Tamashiro VG, Perez HH, Griffin DE. Prospective study of the magnitude and duration of changes in tuberculin reactivity during uncomplicated and complicated measles. Pediatr Infect Dis J. 1987 May;6(5):451-4. doi: 10.1097/00006454-198705000-00007.

  PMID: 3601492 BACKGROUND

• de Vries RD, McQuaid S, van Amerongen G, Yuksel S, Verburgh RJ, Osterhaus AD, Duprex WP, de Swart RL. Measles immune suppression: lessons from the macaque model. PLoS Pathog. 2012;8(8):e1002885. doi: 10.1371/journal.ppat.1002885. Epub 2012 Aug 30.

  PMID: 22952446 BACKGROUND

• de Swart RL, Ludlow M, de Witte L, Yanagi Y, van Amerongen G, McQuaid S, Yuksel S, Geijtenbeek TB, Duprex WP, Osterhaus AD. Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques. PLoS Pathog. 2007 Nov;3(11):e178. doi: 10.1371/journal.ppat.0030178.

  PMID: 18020706 BACKGROUND

• Mina MJ, Metcalf CJ, de Swart RL, Osterhaus AD, Grenfell BT. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 2015 May 8;348(6235):694-9. doi: 10.1126/science.aaa3662. Epub 2015 May 7.

  PMID: 25954009 BACKGROUND

• Ludlow M, Lemon K, de Vries RD, McQuaid S, Millar EL, van Amerongen G, Yuksel S, Verburgh RJ, Osterhaus AD, de Swart RL, Duprex WP. Measles virus infection of epithelial cells in the macaque upper respiratory tract is mediated by subepithelial immune cells. J Virol. 2013 Apr;87(7):4033-42. doi: 10.1128/JVI.03258-12. Epub 2013 Jan 30.

  PMID: 23365435 BACKGROUND

• Ludlow M, de Vries RD, Lemon K, McQuaid S, Millar E, van Amerongen G, Yuksel S, Verburgh RJ, Osterhaus ADME, de Swart RL, Duprex WP. Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus. J Gen Virol. 2013 Sep;94(Pt 9):1933-1944. doi: 10.1099/vir.0.054650-0. Epub 2013 Jun 19.

  PMID: 23784446 BACKGROUND

• Lemon K, de Vries RD, Mesman AW, McQuaid S, van Amerongen G, Yuksel S, Ludlow M, Rennick LJ, Kuiken T, Rima BK, Geijtenbeek TB, Osterhaus AD, Duprex WP, de Swart RL. Early target cells of measles virus after aerosol infection of non-human primates. PLoS Pathog. 2011 Jan 27;7(1):e1001263. doi: 10.1371/journal.ppat.1001263.

  PMID: 21304593 BACKGROUND

• Laksono BM, de Vries RD, McQuaid S, Duprex WP, de Swart RL. Measles Virus Host Invasion and Pathogenesis. Viruses. 2016 Jul 28;8(8):210. doi: 10.3390/v8080210.

  PMID: 27483301 BACKGROUND

• Laksono BM, de Vries RD, Duprex WP, de Swart RL. Measles pathogenesis, immune suppression and animal models. Curr Opin Virol. 2020 Apr;41:31-37. doi: 10.1016/j.coviro.2020.03.002. Epub 2020 Apr 24.

  PMID: 32339942 BACKGROUND

• de Vries RD, de Swart RL. Measles immune suppression: functional impairment or numbers game? PLoS Pathog. 2014 Dec 18;10(12):e1004482. doi: 10.1371/journal.ppat.1004482. eCollection 2014 Dec. No abstract available.

  PMID: 25522010 BACKGROUND

Related Links

• WHO measles key facts
• A 30-fold rise of measles cases in 2023 in the WHO European Region warrants urgent action
• Measles on the rise in the EU/EEA: considerations for public health response

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood sample of max 50ml, and give a nasal swab and mucus sample

MeSH Terms

Conditions

Measles

Condition Hierarchy (Ancestors)

Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Central Study Contacts

Dr C.H. Geurts van Kessel

CONTACT

+31643271384; c.geurtsvankessel@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical microbiologist

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 5, 2025
• Study Start: July 3, 2025
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): July 30, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-11

Locations

NL (1)