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Antibodies, IFN-ɣ, IL-17A, Measles-vaccines, T cells
Background: Measles vaccinations have been suggested to provide immune protection and decreased measles incidence. However, there was a limited study evaluating how the measles vaccine elicits specific immune responses.
Objective: This study aimed to evaluate both humoral and cellular immunity to first-dose measles vaccine Edmonston-Zagreb (EZ) in 9-month-old Indonesian infants.
Methods: A cohort study was conducted on 9-month-old infants who got the first-dose of measles vaccine EZ. Measles-specific immunoglobulin G (IgG) antibody serum levels were measured using plaque-reduction microneutralization assay. Peripheral blood mononuclear cells were stimulated with a measles-specific peptide to identify a cellular immune response. Quantification of CD4+ and CD8+ T-cells producing interferon-gamma (IFN-ɣ) and interleu-kin 17-A (IL-17A) were conducted by flow cytometry. Humoral and cellular immune response parameters were analyzed over time.
Results: The prevalence of seropositivity rates was 85.8% at 1-month after vaccination and 16.67% at 6-months postvaccination. Measles-specific IgG antibodies increased significantly at 1-month after measles vaccination. However, they decreased significantly 6-months after vaccination. IFN-ɣ and IL-17A secreting T-cells increased significantly at 1-month after measles vaccination. Interestingly, a significant decrease of IFN-ɣ and IL-17A secreting CD4+ T cells was noticed 6-months postvaccination compared to IFN-ɣ and IL-17A secreting CD8+ T cells.
Conclusion: Our study suggests that the first-dose measles vaccine on 9-months-old infants seems to induce both humoral and cellular immune responses that decline 6-months after vaccination.
2. Centers for Disease Control and Prevention. Measles (rubeola): history of measles; 2018 [accessed 15 June 2020]. https://www.cdc.gov/measles/about/history.html
3. Fraser-Bell CJ. Global re-emergence of measles-2019 update. Global Biosecurity. 2019; 1(3):1–10. http://doi.org/10.31646/ gbio.43
4. World Health Organization, UNICEF. WHO and UNICEF estimates of immunization coverage; 2020 [accessed 01 Aug 2020]. https://www.who.int/immunization/monitoring_sur-veillance/data/idn.pdf?ua=1
5. Ministry of Health of the Republic of Indonesia. Profil kesehatan Indonesia tahun 2017 [Health profile of Indonesia in 2017]. Jakarta: Ministry of Health of the Republic of Indonesia. https://pusdatin.kemkes.go.id/resources/download/pusda-tin/profil-kesehatan-indonesia/Profil-Kesehatan-Indonesia-tahun-2017.pdf
6. World Health Organization. Measles and rubella surveillance data; 2020 [accessed 20 June 2020]. https://www. who.int/immunization/monitoring_surveillance/burden/vpd/ surveillance_type/active/measles_monthlydata/en/
7. The Straits Times. Indonesia declares end to deadly Papua measles outbreak; 2018 [accessed 15 June 2020]. https://www.straitstimes.com/asia/seasia/indonesia-declares-end-to-deadly-papua-measles-outbreak
8. World Health Organization. The immunological basis for immunization series: module 7: measles: update 2020; 2020 [accessed 29 June 2020].
9. Gans HA, Yasukawa LL, Sung P, Sullivan B, DeHovitz R, Audet S, et al. Measles humoral and cell-mediated immunity in children aged 5–10 years after primary measles immunization administered at 6 or 9 months of age. J Infect Dis. 2013;207:574–82. https://doi.org/10.1093/infdis/jis719
10. Griffin DE. The immune response in measles: virus control, clearance and protective immunity. Viruses. 2016;8:282. https://doi.org/10.3390/v8100282
11. Laksono BM, Grosserichter-Wagener C, de Vries RD, Langeveld SAG, Brem MD, van Dongen JJM, et al. In vitro measles virus infection of human lymphocyte subsets demonstrates high susceptibility and permissiveness of both naive and memory B cells. J Virol. 2018;92:e00131–18. https://doi.org/10.1128/ JVI.00131-18
12. Martins C, Garly ML, Bale C, Rodrigues A, Njie-Jobe J, Benn CS, et al. Measles virus antibody responses in children randomly assigned to receive standard-titer Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age. J Infect Dis. 2014;210:693–700. https://doi.org/10.1093/infdis/jiu117
13. Kurubi J, Vince J, Ripa P, Tefuarani N, Riddell M, Duke T. Immune response to measles vaccine in 6-month-old infants in Papua New Guinea. Trop Med Int Health. 2009;14:167–73. https://doi.org/10.1111/j.1365-3156.2008.02214.x
14. Gans HA, Ren J, Yasukawa LL, Alderson A, Rinki M, DeHovitz R, et al. Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States. J Infect Dis. 2004;190:83–90. https://doi.org/10.1086/421032
15. Pan L, Zhang W, Liang Z, Wu X, Zhu X, Li J, et al. Association between polymorphisms of the cytokine and cytokine receptor genes and immune response to hepatitis B vaccination in a Chinese Han population. J Med Virol. 2012;84:26–33.
16. Njie-Jobe J, Nyamweya S, Miles DJC, van der Sande M, Zaman S, Touray E, et al. Immunological impact of an additional early measles vaccine in Gambian children: responses to a boost at 3 years. Vaccine. 2012;30:2543–50.
17. Nelson AN, Putnam N, Hauer D, Baxter VK, Adams RJ, Griffin DE. Evolution of T cell responses during measles virus infection and RNA clearance. Sci Rep. 2017;7:1–10. https://doi.org/10.1038/s41598-017-10965-z
18. Anichini G, Gandolfo C, Fabrizi S, Miceli GB, Terrosi C, Savellini GG, et al. Seroprevalence to measles virus after vaccination or natural infection in an adult population, in Italy. Vaccines. 2020;8:1–12. https://doi.org/10.3390/vaccines8010066
19. World Health Organization. WHO expert committee on biological standardization, 6th report. Geneva, Switzerland: World Health Organization; 2013. https://www.who.int/biologicals/ expert_committee/TRS_978_61st_report.pdf?ua=1
20. Lochlainn LMN, de Gier B, van der Maas N, van Binnendijk R, Strebel PM, Goodman T, et al. Effect of measles vaccination in infants younger than 9 months on the immune response to subsequent measles vaccine doses: a systematic review and meta-analysis. Lancet Infect Dis. 2019;19:1246–54. https://doi.org/10.1016/S1473-3099(19)30396-2
21. LeBaron CW, Beeler J, Sullivan BJ, Forghani B, Bi D, Beck C, et al. Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment. Arch Pediat Adol Med. 2007;161:294–301. https://doi.org/10.1001/archpedi.161.3.294
22. Hussain H, Akram DS, Chandir S, Khan AJ, Memon A, Halsey NA. Immune response to 1 and 2 dose regimens of measles vaccine in Pakistani children. Hum Vaccines Immunother. 2013;9:2529– 32. https://doi.org/10.4161/hv.25993
23. James SH. Measles, Mumps and rubella viruses. In: Cohen J, Powderly WG, Opal SM, editors. Infectious disease. 4th ed. New York: Elsevier; 2017, p. 1399–1405.
24. Fisker AB, Nebie E, Schoeps A, Martins C, Rodrigues A, Zakane A, et al. A two-center randomized trial of an additional early dose of measles vaccine: effects on mortality and measles antibody levels. Clin Infect Dis. 2018;66:1573–80. https://doi.org/10.1093/cid/cix1033
25. Carazo S, Billard MN, Boutin A, de Serres G. Effect of age at vaccination on the measles vaccine effectiveness and immunogenicity: systematic review and meta-analysis. BMC Infect Dis. 2020;20:251. https://doi.org/10.1186/s12879-020-4870-x
26. Lin WHW, Pan CH, Adams RJ, Laube BL, Griffin DE. Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA. mBio. 2014;5:e01047–14. https://doi.org/10.1128/mBio.01047-14
27. Nakayamada S, Takahashi H, Kanno Y, O’Shea JJ. Helper T cell diversity and plasticity. Curr Opin Immunol. 2012;24:297–302. https://doi.org/10.1016/j.coi.2012.01.014
28. Lin Y, Slight SR, Khader SA. Th17 cytokines and vaccine-induced immunity. Semin Immunopathol. 2010;32:79–90. https://doi.org/10.1007/s00281-009-0191-2
29. Busch E, Kubon KD, Mayer JKM, Pidelaserra-Martí G, Albert J, Hoyler B, et al. Measles vaccines designed for enhanced CD8+ T cell activation. Viruses. 2020;12:242–9.
30. Bautista-López NL, Vaisberg A, Kanashiro R, Hernández H, Ward BJ. Immune response to measles vaccine in Peruvian children. Bull World Health Organ. 2001;79:1038–46.