Journal of Clinical Immunology

, Volume 30, Issue 4, pp 574–582 | Cite as

Humoral and Cellular Immune Responses to Measles and Tetanus: The Importance of Elapsed Time Since Last Exposure and the Nature of the Antigen

  • Patricia O. Viana
  • Erika Ono
  • Maristela Miyamoto
  • Reinaldo Salomao
  • Beatriz T. Costa-Carvalho
  • Lily Y. Weckx
  • Maria Isabel de Moraes-Pinto



This study aims to assess the cellular and humoral immune response pre- and post-vaccine rechallenge in healthy adults with previous exposure to measles (virus or vaccine) and different time intervals since last tetanus vaccine.


Humoral immunity was tested by ELISA, and cellular immunity was tested by intracellular interferon gamma detection after in vitro stimulation with antigens.


While cellular immunity was comparable among vaccinated individuals and those who had measles, higher antibody levels were found in those who had the disease in the past. Both antibodies and CD4+ T cell tetanus immune responses depended on elapsed time since last immunization. Following a vaccine booster, an increase in cellular immunity and antibodies was observed to both tetanus and measles. Measles humoral response was much more intense among individuals previously exposed to a wild virus.


In an era when natural boosters are less frequent, an immune surveillance might be necessary to investigate waning immunity as occurs for tetanus.


Measles tetanus cellular immunity antibody immunologic memory 



This study was funded by the Fundação de Auxílio à Pesquisa do Estado de São Paulo (FAPESP), a Brazilian funding agency (05/57802-5 and 05/57571-3).


  1. 1.
    Plotkin SA. Vaccines: past, present and future. Nat Med. 2005;11(4):S5–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Kaufmann SHE. The contribution of immunology to the rational design of novel antibacterial vaccines. Nat Rev Microbiol. 2007;5(7):491–504.CrossRefPubMedGoogle Scholar
  3. 3.
    Maino VC, Maecker HT. Cytokine flow cytometry: a multiparametric approach for assessing cellular immune responses to viral antigens. Clin Immunol. 2004;110:222–31.CrossRefPubMedGoogle Scholar
  4. 4.
    World Health Organization (WHO): Measles imported cases in Santa Catarina, Brazil. EID Weekly Updates: emerging and reemerging infection diseases, Region of the Americas. Accessed 28 Sep 2009.
  5. 5.
    Borrow R, Balmer P, Roper MH. The immunological basis for immunization series. Module 3: tetanus. Geneva: World Health Organization; 2006. p. 1–52.Google Scholar
  6. 6.
    Gaines H, Biberfeld G. Measurement of lymphoproliferation at the single-cell level by flow cytometry. Methods Mol Biol. 2000;134:243–55.PubMedGoogle Scholar
  7. 7.
    Pala P, Hussell T, Openshaw PJM. Flow cytometric measurement of intracellular cytokines. J Immunol Methods. 2000;243:107–24.CrossRefPubMedGoogle Scholar
  8. 8.
    Kristiansen M, Aggerbeck H, Heron I. Improved ELISA for determination of anti-diphtheria and/or anti-tetanus antitoxin antibodies in sera. Acta Pathol Microbiol Scand. 1997;105:843–53.Google Scholar
  9. 9.
    de Moraes-Pinto MI, Almeida ACM, Kenj G, Filgueiras TE, Tobias W, Santos AMN, et al. Placental transfer and maternally acquired neonatal Igg immunity in HIV infection. J Infect Dis. 1996;173:1077–84.PubMedGoogle Scholar
  10. 10.
    Chen RT, Markowitz LE, Albrecht P, Stewart JA, Mofenson LM, Preblud SR, et al. Measles antibody: reevaluation of protective titers. J Infect Dis. 1990;162:1036–42.PubMedGoogle Scholar
  11. 11.
    Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L, et al. Loss of vaccine-induced immunity to varicella over time. N Engl J Med. 2007;356(11):1121–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Lu CY, Ni YH, Chiang BL, Chen PJ, Chang MH, Chang LY, et al. Humoral and cellular immune responses to a hepatitis B vaccine booster 15–18 years after neonatal immunization. J Infect Dis. 2008;197:1419–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Miller JD, van der Most RG, Akondy RS, Glidewell JT, Albott S, Masopust D, et al. Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity. 2008;28(5):710–22.CrossRefPubMedGoogle Scholar
  14. 14.
    Costantini A, Mancini S, Giuliodoro S, Butini L, Regnery CM, Silvestri G, et al. Effects of cryopreservation on lymphocyte immunophenotype and function. J Immunol Methods. 2003;278:145–55.CrossRefPubMedGoogle Scholar
  15. 15.
    Suni MA, Picker LJ, Maino VC. Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. J Immunol Methods. 1998;212:89–98.CrossRefPubMedGoogle Scholar
  16. 16.
    Nanan R, Rauch A, Kämpgen E, Niewiesk S, Kreth HW. A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles. J Gen Virol. 2000;81:1313–9.PubMedGoogle Scholar
  17. 17.
    Ovsynnikova IG, Dhiman N, Jacobson RM, Vierkant RA, Poland GA. Frequency of measles virus-specific CD4+ and CD8+ T cells in subjects seronegative or highly seropositive for measles vaccine. Clin Diagn Lab Immunol. 2003;10(3):411–6.Google Scholar
  18. 18.
    Christenson B, Bottinger M. Measles antibody: comparison of long-term vaccination titres, early vaccination titres and naturally acquired immunity to and booster effects on the measles virus. Vaccine. 1994;12(2):129–33.CrossRefPubMedGoogle Scholar
  19. 19.
    Caglar K, Karakus R, Aybay C. Determination of tetanus antibodies by double-antigen enzyme-linked immunosorbent assay in individuals of various age groups. Eur J Clin Microbiol Infect Dis. 2005;24:523–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Lambert PH, Liu M, Siegrist CA. Can successful vaccines teach us how to induce efficient protective immune responses? Nat Med. 2005;11(4):S54–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Mossong J, Nokes DJ, Edmunds WJ, Cox MJ, Ratnam S, Muller CP. Modeling the impact of subclinical measles transmission in vaccinated populations with waning immunity. Am J Epidemiol. 1999;150:1238–49.PubMedGoogle Scholar
  22. 22.
    LeBaron CW, Beeler J, Bradley J, Sullivan BJ, Forghani B, Bi D, et al. Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment. Arch Pediatr Adolesc Med. 2007;161:294–301.CrossRefPubMedGoogle Scholar
  23. 23.
    Davidkin I, Jokinen S, Broman M, Leinikki P, Peltola H. Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up. J Infect Dis. 2008;197(7):950–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Putz MM, Bouche FB, Swart RL, Muller CP. Experimental vaccines against measles in a world of changing epidemiology. Int J Parasitol. 2003;33:525–45.CrossRefPubMedGoogle Scholar
  25. 25.
    Manz RA, Arce S, Cassese G, Hauser AE, Hiepe F, Radbruch A. Humoral immunity and long-lived plasma cells. Curr Opin Immunol. 2002;14(4):517–21.CrossRefPubMedGoogle Scholar
  26. 26.
    Slifka MK, Ahmed R. Long-lived plasma cells: a mechanism for maintaining persistent antibody production. Curr Opin Immunol. 1998;10(3):252–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Patricia O. Viana
    • 1
  • Erika Ono
    • 1
  • Maristela Miyamoto
    • 1
  • Reinaldo Salomao
    • 2
  • Beatriz T. Costa-Carvalho
    • 3
  • Lily Y. Weckx
    • 1
  • Maria Isabel de Moraes-Pinto
    • 1
  1. 1.Division of Pediatric Infectious Diseases, Department of PediatricsFederal University of São PauloSão PauloBrazil
  2. 2.Division of Infectious DiseasesFederal University of São PauloSão PauloBrazil
  3. 3.Division of Allergy and Clinical Immunology, Department of PediatricsFederal University of São PauloSão PauloBrazil

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