Duration of Measles Vaccine–Induced Antibody
• JID 2004:189 (Suppl 1) • S123
S U P P L E M E N T A R T I C L E
Persistence of Vaccine-Induced Antibody to Measles
26–33 Years after Vaccination
Mark S. Dine,1Sonja S. Hutchins,2Ann Thomas,2,aIrene Williams,3William J. Bellini,3and Stephen C. Redd4
1Private practice, Cincinnati, Ohio;
for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia
2National Immunization Program,
3National Center for Infectious Diseases, and
Because measles-specific antibody titer after vaccination is lower than after natural infection, there is concern
that vaccinated persons may gradually lose protection from measles. To examine the persistence of vaccine-
induced antibody, participants of a vaccine study in 1971, with documentation of antibody 1–7 years after
vaccination, were followed up in 1997–1999 to determine the presence and titer of measles antibody. Of the 56
participants (77% were 2-dose recipients), all had antibodies detected by the plaque reduction neutralization
(PRN) antibody assay an average of 26–33 years after the first or second dose of measles vaccine; 92% had a
PRN titer considered protective (11:120). Baseline hemagglutination inhibition antibody titer in 1971 strongly
predicted follow-up PRN antibody titer (). Persistence of antibody in these primarily 2-dose recipients
P ! .001
mission in the United States, a high level of protection
against measles in the population must be sustained
[1–3]. A potential obstacle to sustaining this high level
is waning of vaccine-induced protection over time, or
secondary vaccine failure [4–7]. Because measles-spe-
cific antibody titer after vaccination is lower than after
natural infection, there is concern that vaccinated per-
sons may gradually lose protection from measles. Sec-
ondary vaccine failure, in contrast to primary vaccine
failure (no protection after vaccination), is a concern
because of the potential insidious challenge to measles
elimination. For instance, if vaccine-induced immu-
nity waned to nonprotective levels in a high propor-
tion of vaccinated adults, the level of population pro-
tection might decline to allow recurrence of endemic
disease. By means of statistical modeling, Mossong et
Presented in part: 34th National Immunization Conference, 5–8 July 2000,
aPresent affiliations: Office of Disease Prevention and Epidemiology, Oregon
Department of Human Services, Portland (A.T.); National Center for Environmental
Health, Centers for Disease Control and Prevention, Atlanta (S.R.).
Reprints or correspondence: Dr. Sonja S. Hutchins, National Immunization
Program, Mailstop E-61, Centers for Disease Control and Prevention, 1600 Clifton
Road, Atlanta, GA 30333 (firstname.lastname@example.org).
The Journal of Infectious Diseases
? 2004 by the Infectious Diseases Society of America. All rights reserved.
al.  predicted waning of vaccine-induced immunity
25 years after immunization.
Isolated cases of measles inpersonswithdocumented
seroconversion after vaccination have been reported[4,
6, 7]. These secondary vaccine failures among adults
in the United States, Canada, and China are of concern
and provide evidence that vaccine-induced protection
may wane. However, the magnitude of the problem
seems small. The number of reported measles cases in
the United States has been at record low levels since
1996, and the number of reported cases in adults has
been very small (32 cases in persons ?20 years of age
in 1999). Though a small number, measles cases in
vaccinated adults (22% of cases in adults) suggest that
waning vaccine-induced protection may explain some
vaccine failures [9, 10].
Although waning vaccine-induced immunity does
occur, population-based prevalence is not known inthe
protection among adults. The third National Health
ducted during 1988–1994, found that 93% of partici-
pants aged ?6 years had measles antibody . This
finding suggests that measles immunity in the United
States is high. However, measlesvaccinationhistorywas
not available for NHANES participants and could not
be linked with seroprevalence results. Even if vaccina-
by guest on November 11, 2015
S130 • JID 2004:189 (Suppl 1) • Dine et al.
among 2-dose recipients, among whom one-half had received
the first dose at age !1 year. Our findings suggest that persons
who have received either a single dose or 2 doses of vaccine a
mean of 26–33 years before may still have detectable neutral-
izing antibody, and nearly all may still have titers considered
to be protective (11:120). The persistence of antibody in this
diverse group of vaccine recipients supports the current elim-
ination strategy to achieve high population immunity with 2
doses of measles vaccine.
Special thanks to all of the study participants for their will-
ingness to participant and take time from their busy schedules
many decades after the initial study in 1971, and to the Visiting
Nurses Association for interviewing and collecting blood. In
addition, special thanks to Mary McCauley for editorial advice
and to Mark Papania and Jane Seward for scientific and edi-
1. Hinman AR, Orenstein WA, Papania MJ. Evolution of measles elim-
ination strategies in the United States. J Infect Dis 2004;189(Suppl 1):
2. Katz SL, Hinman AR. Summary and conclusions: measles elimination
meeting, 16–17 March 2000. J Infect Dis 2004;189(Suppl 1):43–7.
3. Centers for Disease Control and Prevention. Measles prevention.
MMWR Morb Mortal Wkly Rep 1989;38(SS-9):1–18.
4. Markowitz LE, Preblud SR, Fine PE, Orenstein WA. Duration of live
measles vaccine-induced immunity. PediatrInfectDisJ1990;9:101–10.
5. Hutchins SS, Bellini W, Coronado V, Jiles R, Wooten K, Deladisma A.
Population immunity to measles in the United States, 1999. J Infect
Dis 2004;189(Suppl 1):91–7.
6. Mathias RG, Merrison WG, Arcand TA, et al. The role of secondary
vaccine failures in measles outbreaks. AmJ PublicHealth1989;79:475–8.
7. Reyes MA, Franky DeBorrero M, Roa J, et al. Measles vaccine failure
after documented seroconversion. Pediatr Infect Dis J 1987;6:848–51.
8. Mossong J, Nokes DJ, Edmunds WJ, et al. Modeling the impact of
subclinical measles transmissioninvaccinatedpopulationswithwaning
immunity. Am J Epidemiol 1999;150:1238–49.
9. Centers for Disease Control and Prevention. Measles—United States,
1999. MMWR Morb Mortal Wkly Rep 2000;49:557–60.
10. Atkinson W. Measles. In: Atkinson W, Murphy L, Humiston SG, et
al, eds. Epidemiology and prevention of vaccine-preventable diseases.
7th ed. Atlanta: Centers for Disease Control and Prevention, 2002.
11. Hutchins SS, Redd S, Schrag S. National serologic survey of measles
immunity among persons ?6 years of age or older, 1988–1994. Med-
scape General Medical Journal 2001;3:E5. Available at: http://www
12. Linneman CC Jr, Dine MS, Bloom JE, Schiff GM. Measles antibody
in previously immunized children. Am J Dis Child 1972;124:53–7.
13. Albrecht P, Herrmann K,BurnsGR.Roleofvirusstraininconventional
and enhanced measles plaque neutralizationtest. JVirolMethods1981;
14. Hummel KB, Erdman DD, Heath J, Bellini WJ. Baculovirusexpression
of the nucleoprotein gene of measles virus and utility of the recom-
binant protein in diagnostic enzyme immunoassays. J Clin Microbiol
15. Ratnam S, Gadag V, West R, et al. Comparison of commercial enzyme
immunoassay kits with plaque reduction neutralization test for detec-
tion of measles virus antibody. J Clin Microbiol 1995;33:811–5.
16. Chen RT, Markowitz LE, Albrecht P, et al. Measles antibody: reeval-
uation of protective titers. J Infect Dis 1990;162:1036–42.
17. Brunell PA. Measles control in the 1990s: measles serology. Geneva:
World Health Organization, 1990; document no. WHO/EPI/Gen/90.4.
18. Samb B, Aaby P, Whittle HC, et al. Serologic status and measles attack
rates among vaccinated and unvaccinated children in rural Senegal.
Pediatr Infect Dis J 1995;14:203–9.
19. De Serres G, Boulianne N, Ratnam S, et al. Effectiveness of vaccination
at 6 to 11 months of age duringan outbreakofmeasles.Pediatrics1996;
20. Mehta C, Patel N. StatXact 3 for windows. Cambridge, MA: Cytel
Software Corporation, 1996.
21. Mehta C, Patel N. LogXact for windows. Cambridge, MA: Cytel Soft-
ware Corporation, 1996.
22. Krugman S, Giles JP, Friedman H, et al. Studies on immunity to mea-
sles. J Pediatr 1965;66:471–88.
23. Krugman S. Present status of measles and rubella immunization in the
United States: a medical progress report. J Pediatr 1977;90:1–12.
24. Krugman S. Further-attenuated measles vaccine: characteristics and
use. Rev Infect Dis 1983;5:477–81.
25. Markowitz LE, Albrecht P, Orenstein WA, et al. Persistence of measles
antibody after revaccination. J Infect Dis 1992;166:205–8.
26. Ward BJ, Boulianne N, Ratnam S, et al. Cellular immunity in measles
vaccine failure: demonstration of measles antigen—specific lympho-
proliferative responses despite limited serum antibodyproductionafter
revaccination. J Infect Dis 1995;172:1591–5.
27. Bautista-Lopez N, Ward BJ, Mills E, et al. Development and durability
of measles antigen—specific lymphoproliferative response after MMR
vaccination. Vaccine 2000;18:1393–401.
28. Anders JF, Jacobson RM, Poland GA. Secondary failureratesofmeasles
vaccines: a metaanalysis of published studies. Pediatr Infect Dis J
29. Stetler HC, Orenstein WA, Bernier RH. Impact of revaccinating chil-
30. LeBaron C, Beeler J, Redd S, et al. Immunogenicity and adverse events
associated with the 2nd dose of MMR vaccine (abstract no. H78b). In:
Program and abstracts of the 36th Interscience Conference on Anti-
microbial Agents and Chemotherapy. Washington, DC: American So-
ciety for Microbiology, 1996.
31. Redd SC, Markowitz LE, Katz SL. Measles vaccine. In: Plotkin SA,
Orenstein WA, eds. Vaccines. Philadelphia:WBSaunders,1999:222–66.
by guest on November 11, 2015