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Cellular Immunity to Mumps Virus in Young Adults 21 Years after Measles-Mumps-Rubella Vaccination

  1. Sari Jokinen,
  2. Pamela Österlund,
  3. Ilkka Julkunen and
  4. Irja Davidkin
  1. Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
  1. Reprints or correspondence: Sari Jokinen, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland (sari.jokinen{at}ktl.fi).
 
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Abstract

Background. Measles-mumps-rubella (MMR) vaccination has decreased the incidence of measles, mumps, and rubella virus infections in several countries. However, the persistence of MMR vaccine-induced immunity in the absence of endemic infection has remained unknown.

Methods. The persistence of cellular and humoral immunity to mumps virus was studied in 50 individuals (group A) who had been vaccinated twice with MMR vaccine during early childhood and were followed up for 21 years after their first vaccination. Eleven individuals (group B) with naturally acquired immunity to mumps virus were studied for comparison.

Results. Anti-mumps virus IgG antibodies were detectable (titer ⩾230) in 72% of the vaccinees. A mumps antigen-specific lymphoproliferative response (defined as a stimulatory index [SI] ⩾3) was observed in 98% of group A subjects (mean±SD SI, 26±30 [range, 0.5–252]) and in 100% of group B subjects (mean±SD SI, 22±27 [range, 5–123]). Significant mumps antigen-specific interferon-γ production was detected in 73% of subjects in both groups A and B, and interleukin-10 production was detected in 40% and 36% of group A and B subjects, respectively.

Conclusions. All presently seronegative vaccinees (n = 14) had mumps antigen-specific lymphoproliferative responses, and only 1 of the seropositive vaccinees (n = 36) was devoid of detectable cellular immunity. The results suggest a very long persistence of vaccine-induced anti-mumps virus cellular immunity.

More than half of the countries in the world use mumps vaccine in their national immunization program. Most of these countries implement a 2-dose measles-mumps-rubella (MMR) vaccination schedule; therefore, at present certain countries (such as Finland) no longer have indigenous mumps [1, 2]. In these countries, the immunity of their younger population depends on vaccinations solely, and thus it has become particularly important to study the duration of vaccine-induced immunity to mumps virus. If vaccine-induced immunity wanes, vaccinated individuals could eventually become unprotected, and thus clinical mumps cases would become more common in adults. Mumps virus infection is relatively benign during early childhood but is clearly more severe in adults [3], although complications seem to be less common in vaccinated individuals [4]. Vaccination coverage of 90% of the population is believed to provide herd immunity to mumps virus [5]; however, the recent epidemic in the United States spread extensively, and even twice-vaccinated individuals became infected [6].

Natural infection with mumps virus is thought to confer lifelong protection; however, mumps virus reinfections do seem to occur [7, 8], although some of the presumed reinfections are known to have other causes than mumps virus [9]. Mumps seropositivity rates and antibody titers peak shortly after the first and second MMR vaccinations and then decline rapidly within a year after the first dose and at a slower pace after the second dose [10]. Mathematical models predict that, in populations that do not encounter periodic subclinical natural booster infections due to circulating wild-type virus, antibody titers continue to decline [11]. Protective anti-mumps virus antibody levels have remained undetermined.

Waning of anti-mumps virus antibodies in the vaccinated population raises the question of whether the cellular immunity of vaccinees wanes as well. Not all vaccinees undergo seroconversion, but mumps vaccine is known to also induce cell-mediated immunity in infants who show limited humoral immune responses [12]. In a study by Gans et al. [12], approximately two-thirds of the vaccinees who did not seroconvert developed memory T cell immunity to mumps virus. At present, it is not known whether a humoral or cellular immune response is more important for protective immunity to mumps virus [4]. However, mumps is not known to be a problem in immunocompromised children [4], and patients with agammaglobulinemia experience a mumps virus infection that produces typical clinical symptoms [13].

To date, only a few studies have been conducted to study the persistence of vaccine-induced immunity to mumps virus [10, 12, 14,17]. In particular, the duration of vaccine-induced cellular immunity to mumps virus has remained poorly characterized. In the present study, we have analyzed the persistence of humoral and cell-mediated immune responses to mumps virus in a cohort of individuals who had received their first MMR vaccine dose 21 years ago at the age of 1.5 or 6 years and their second dose at the age of 6 or 11–13 years, respectively [1]. Because mumps virus infection was eliminated from Finland almost 10 years ago [1], this cohort represents a group of people who have likely avoided natural booster infections [18].

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Subjects, Materials, and Methods

Study subjects. Invitations to participate in the present study were sent to 118 individuals (22–23 or 27–28 years of age) belonging to an MMR vaccination cohort that includes 350 individuals whose levels of antibody to measles, mumps, and rubella virus have been monitored since their first MMR vaccination, which was given 21 years earlier [1]. Emphasis was placed on individuals who were either seronegative or had low antibody titers in 2002, when 20-year follow-up tests were done (authors' unpublished data). Fifty of these MMR-vaccinated young adults (group A) joined the study, and blood samples were collected to analyze humoral and cellular immune responses to mumps antigen. The study subjects had received their first dose of MMRII vaccine (containing the Moraten strain of measles virus, the Jeryl Lynn strain of mumps virus, and the RA27/3 strain of rubella virus; Merck) in 1982, at the age of 1.5 years (group A-1y; n = 27; 16 females and 11 males) or 6 years (group A-6y; n = 23; 10 females and 13 males), and their second dose at the age of 6 or 11–13 years, respectively. Ninety-three percent of group A-1y subjects and 83% of group A-6y subjects had undergone seroconversion after the first MMR dose, and 100% and 91%, respectively, had become seropositive after the second vaccine dose. A positive control group (group B) included 11 nonvaccinated, mumps virus-seropositive individuals (40–63 years of age) who had experienced a clinical mumps virus infection during their childhood. Ten cord blood specimens obtained from the Kätilöopisto Maternity Hospital in Helsinki, Finland, comprised a negative control group (group C) for the lymphoproliferative and cytokine tests. The study protocol was approved by the HUS (Hospital District of Helsinki and Uusimaa) Ethical Committee of Epidemiology and Public Health in Helsinki, Finland, and all study subjects or their parents provided informed consent for the present study.

Sample collection. Blood samples for antibody determinations were collected in 7-mL BD Vacutainer gel tubes. Blood samples for lymphoproliferation and cytokine assays were collected in either 8-mL BD Vacutainer CPT tubes or 10-mL VenoJect lithium heparin tubes (Terumo Europe).

Serological assays. IgG antibodies to mumps virus were measured using the Enzygnost Anti-Parotitis-Virus/IgG test (Dade Behring). The Enders strain of mumps virus is used as the antigen in this assay. On the basis of the manufacturer's instructions, serum specimens with mumps virus-specific antibody titers ⩾230 were considered to be positive.

Lymphoproliferative assay. Mumps antigen for the assays was prepared from mumps virus (Enders strain) grown in 8-day-old embryonated chicken eggs, collected at 5 days after infection, and purified in sucrose gradients as described elsewhere [19]. The protein composition of the antigen was analyzed by 8% SDS-PAGE and was found to contain all mumps virus structural proteins. For each study subject, quadruplicate wells of 100, 50, or 20 ng/mL UV light-inactivated purified mumps virus; 0.5 µg/mL phytohemagglutinin (PHA; Leucoagglutinin PHA-L; Sigma) as a positive control; and medium as a negative control were prepared in a volume of 100 µL/well in 96-well round-bottom microtiter tissue culture plates (Cell-star; Greiner Bio-One International) and stored at −70°C until use. The medium used was RPMI 1640 (Sigma) supplemented with 2 mmol/L l-glutamine (Fluka), 100 U/mL penicillin (Orion), 100 µg/mL streptomycin (Sigma), and 10% human AB serum (Finnish Red Cross Blood Service). The mumps antigen and the positive and negative control antigens were devoid of endotoxins (<0.125 IU/mL), as determined by the limulus test.

Peripheral blood mononuclear cells (PBMCs) were separated from the blood collected in the BD Vacutainer CPT tubes and washed according to the manufacturer's instructions. Ficoll-Paque Plus (Amersham Biosciences) density gradient was used to separate the PBMCs from the blood samples collected in the VenoJect lithium heparin tubes. PBMCs were resuspended at a concentration of 1 × 106 cells/mL in RPMI 1640 medium supplemented as described above.

PBMCs were plated in a volume of 100 µL/well (1 × 105 cells/well) in the prepared culture plates. After culturing for 5 days at 37°C in 4% CO2, 1 µCi of 3H-tritiated thymidine (Amersham Biosciences) was added to the wells. The PBMCs were cultured for an additional 16–18 h before being collected on glass fiber filters (Wallac) by use of a 96-well cell harvester (TomTek). The amount of incorporated radioactivity in each well was measured as counts per minute in a scintillation counter (Wallac MicroBeta; PerkinElmer Life Sciences). An antigen-specific stimulation index (SI) was defined as the ratio of the mean counts per minute for the stimulated wells to the mean counts per minute for the unstimulated wells for each antigen concentration separately. The results for the antigen concentration with the highest SI values were used for analysis [20]. An SI ⩾3 was considered to be indicative of a positive lymphoproliferative response, on the basis of the mean±SD SI for the response in cord blood mononuclear cells.

Cytokine measurements. Tissue culture plates (24 well; Greiner Bio-One) were prepared in advance and stored at −70°C until use. For each study subject, duplicate wells of UV light-inactivated mumps virus (final concentration, 50 ng/mL), a well of PHA (final concentration, 0.5 µg/mL), and a negative control well containing RPMI 1640 medium supplemented as described above were prepared in a volume of 500 µL/well. Cells were plated in a volume of 500 µL/well (2 × 105 cells/well) in the prepared culture plates and cultured for 5 days at 37°C in 4% CO2. The supernatants were collected and stored at −70°C until testing. Interferon (IFN)-γ and interleukin (IL)-10 levels in cell culture supernatants were determined by the IFN-γ Eli-Pair (Diaclone Research) and Pharmingen IL-10 ELISA (BD Biosciences) assays. Cutoff values (mean of blank wells plus 3 SDs) for the tests were 9 and 12 pg/mL for IFN-γ and IL-10, respectively. Mumps antigen-induced IFN-γ and IL-10 production was considered to be significant if the ratio of mumps antigen-stimulated production to unstimulated production was ⩾2.

Statistical analysis. Correlations were calculated using Pearson's test. Significant differences were determined using Welch's analysis of variance test for antibody levels and Tukey's studentized range test for lymphoproliferative responses and cytokine production. All values were logarithmically transformed (ln) to obtain a normal distribution for analysis.

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Results

Mumps virus-specific IgG antibodies. To determine the persistence of mumps vaccine-induced (group A) and natural infection-induced (group B) humoral immunity, serum anti-mumps virus antibody levels were measured by ELISA. The geometric mean titer (GMT) of anti-mumps virus IgG antibodies in group A subjects was 331 (SD, 367 [range, <230–2500]), and there was no difference between group A-1y and group A-6y. The GMT for group B was significantly higher (GMT ± SD, 1619±1116 [range, 750–5800]; P = .0032). Anti-mumps virus IgG antibodies were detected in 21 (78%) of the 27 subjects and in 15 (65%) of the 23 subjects in groups A-1y and A-6y, respectively. All 11 subjects (100%) in group C were seropositive.

Mumps antigen–specific lymphoproliferation. Significant lymphoproliferative responses (SI ⩾3) to mumps antigen were seen in 25 (96%) of the 26 subjects in group A-1y and in all subjects in group A-6y and in group B (control) (table 1). The PBMC sample from 1 subject in group A-1y and from 1 subject in group A-6y responded neither to mumps antigen nor to PHA stimulation, and thus their results were excluded from the comparisons. It is noteworthy that all presently seronegative vaccinees (IgG titer <230) had significant mumps antigen-specific lymphoproliferative responses. There was no correlation between anti-mumps virus IgG antibody levels and mumps antigen-specific lymphoproliferative responses in group A (R = 0.110) (figure 1). A weak negative—although not significant—correlation was seen in group B (R = −0.307).

Figure 1
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Figure 1

No significant correlation between anti-mumps virus IgG antibody level and mumps antigen-specific lymphoproliferative response 21 years after the first measles-mumps-rubella (MMR) dose in individuals who had been vaccinated twice with MMR vaccine during early childhood (group A; n = 50; white squares and solid line) or in nonvaccinated individuals with naturally acquired immunity to mumps virus (group B; n = 11; black triangles and dashed line) (R = 0.110 and R = −0.307, respectively; Pearson's test). SI, stimulation index.

The intensity of the mumps antigen-specific lymphoproliferative responses in groups A and B did not differ significantly (mean±SD SI, 26±30 [range, 0.5–252] and 22±27 [range, 5–123], respectively) (figure 2). There was no difference between groups A-1y and A-6y with respect to proliferative response. On average, the seronegative subjects (n = 14) in group A showed a higher mumps antigen-specific lymphoproliferative response than did the seropositive subjects (n = 34) (mean ± SD SI, 37±35 [range, 3–138] and 22±27 [range, 0.5–252], respectively), but the difference was not statistically significant.

Figure 2
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Figure 2

Similarity of mumps antigen-specific lymphoproliferative responses between vaccinated subjects (group A; n = 48) and nonvaccinated subjects with naturally acquired immunity to mumps virus (group B; n = 11). Samples of cord blood mononuclear cells comprised a negative control group (group C; n = 10). Differences were assayed for significance using Tukey's studentized range test. Data are shown as box plots representing the mean value and the 10th, 25th, 75th, and 90th percentiles; circles indicate outlying values. PHA, phytohemagglutinin; SI, stimulation index.

Mumps antigen–induced IFN-γ and IL-10 production. Cytokine production assays were done in all but 2 study subjects (both in group A-6y), whose samples could not be analyzed because of the low number of PBMCs acquired. Significant amounts of IFN-γ were produced by 21 (78%) of 27, 14 (67%) of 21, and 8 (73%) of 11 mumps antigen-stimulated PBMC samples from subjects in groups A-1y, A-6y, and B, respectively (table 1). PBMC samples from 8 (61%) of 13 seronegative subjects and 27 (77%) of 35 seropositive subjects in group A produced IFN-γ.

The mean level of mumps antigen-specific IFN-γ production did not differ significantly between groups A and B (mean ± SD, 107±763 [range, <9–6129] and 202±1194 [range, <9–4578] pg/mL, respectively) (figure 3). Interestingly, when group A was analyzed by age, it was observed that IFN-γ production in group A-6y was significantly lower than that in group A-1y (mean±SD, 47±240 [range, <9–1032] and 202±1060 [range, <9-6129] pg/mL, respectively; P = .0271). Mumps antigen-specific IFN-γ production was also sex dependent in group A, such that females produced significantly more IFN-γ than did males (mean±SD, 230±768 [range, <9–4050] and 68±694 [range, <9–6129] pg/mL, respectively; P = .0315). In group A, IFN-γ production did not differ significantly between seronegative and seropositive subjects (mean ± SD, 69±919 [range, <9–6129] and 125±702 [range, <9–4050] pg/mL, respectively).

Figure 3
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Figure 3

No statistically significant difference in mean levels of mumps antigen-stimulated and phytohemagglutinin (PHA)-stimulated interferon (IFN)-γ production between vaccinated subjects (group A; n = 48) and nonvaccinated subjects with naturally acquired immunity to mumps virus (group B; n = 11). Samples of cord blood mononuclear cells comprised a negative control group (group C; n = 10). Differences were assayed for significance using Tukey's studentized range test. Data are shown as box plots representing the mean value and the 10th, 25th, 75th, and 90th percentiles; asterisks indicate outlying values.

Significant amounts of IL-10 were produced by 19 (40%) of 48 and 4 (36%) of 11 mumps antigen-stimulated PBMC samples from subjects in groups A and B, respectively (table 1). The mean levels of IL-10 produced in groups A and B were not significantly different (mean±SD, 44±108 [range, <12–1152] and 75±133 [range, 23–551] pg/mL, respectively) (figure 4). However, when group A was analyzed by age, it was observed that group A-6y had significantly lower IL-10 production than did groups A-1y and B (mean±SD, 25±42 [range, <12–310], 63±144 [range, <12–1152], and 75±133 [range, 23–551] pg/mL, respectively; P = .0168). Unlike IFN-γ production, there was no significant sex-dependent difference in IL-10 production in group A (mean±SD, 51±149 [range, <12–1152] pg/mL for females and 35±54 [range, <12–310] pg/mL for males). Neither was there any significant difference in IL-10 production between the seropositive and seronegative subjects in group A (mean±SD, 49±133 [range, <12–1152] and 29±41 [range, <12–147] pg/mL, respectively). Only 1 seropositive vaccinee was devoid of any signs of cellular immunity.

Figure 4
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Figure 4

No statistically significant difference in mean levels of unstimulated, phytohemagglutinin (PHA)-stimulated, and mumps antigen-stimulated interleukin (IL)-10 between vaccinated subjects (group A; n = 48) and nonvaccinated subjects with naturally acquired immunity to mumps virus (group B; n = 11). Samples of cord blood mononuclear cells comprised a negative control group (group C; n = 10). Differences were assayed for significance using Tukey's studentized range test. Data are shown as box plots representing the mean value and the 10th, 25th, 75th, and 90th percentiles; circles indicate outlying values.

Table 1
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Table 1 Mumps antigen-specific lymphoproliferative responses, interferon (IFN)-γ production levels, and interleukin (IL)-10 production levels in relation to anti-mumps virus IgG antibody levels in measles-mumps-rubella (MMR) vaccinated subjects and in nonvaccinated subjects with naturally acquired immunity to mumps virus.

A strong positive correlation was seen between mumps antigen-stimulated IFN-γ and IL-10 production for both groups A and B (R = 0.664 and R=0.897, respectively). Interestingly, in group A-6y (R = 0.811) and in the female vaccinees of group A (R = 0.860), there was almost as high a correlation between individual IFN-γ and IL-10 production as in group B.

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Discussion

The most interesting finding of the present study was that all but 1 of the study subjects who had been vaccinated twice with MMR vaccine during early childhood had detectable mumps antigen-specific cellular immune responses 21 years after the first MMR vaccine dose. The possibility of natural booster infections after vaccination is very low, because, after the initiation of the 2-dose MMR vaccination program in Finland in 1982, the incidence of mumps virus infection decreased dramatically [18]. Finland has been free of indigenous mumps virus infections for the last 10 years, and the latest epidemic (75 cases) occurred in 1987 [2].

Mumps antigen-specific lymphoproliferative responses were evident in all but 1 vaccinated individual, and the vaccinees showed lymphoproliferative responses as high as those in the naturally immune individuals. In addition, mumps antigen-induced IFN-γ and IL-10 production in the vaccinees was equal to that in the individuals with naturally acquired immunity. The proinflammatory cytokine IFN-γ is a good indicator of antigen-specific cellular immunity [17]. The anti-inflammatory cytokine IL-10 may be important in maintaining sufficient humoral or Th2 immune responses during antigen stimulation [21]. The strength of the cell-mediated immunity did not correlate with serum anti-mumps virus IgG antibody levels, indicating that the different arms of immunity develop apart from each other. These results suggest a very long persistence of vaccine-induced cellular immunity and indicate that vaccine-induced cell-mediated immunity and that induced by natural infection develop equally well. An interesting observation is that there was a strong positive correlation between IFN-γ and IL-10 production, which may indicate that good responders produce multiple cytokines simultaneously in response to antigen stimulation.

The mumps virus component of most MMR vaccines has been shown to be a fairly good immunogen, one that usually leads to seroconversion rates of >90% [3, 22–24]. In our previous study, the seroconversion rate for mumps virus was 86% after the first MMR vaccine dose and was 95% after the second dose [10]. Levels of vaccine-induced mumps virus-specific antibodies are on average lower than those seen in individuals who have had a natural infection [25]. In addition, previous investigations we have conducted have shown that 23% of the twice-vaccinated individuals had become seronegative for mumps virus-specific antibody 20 years after the first MMR vaccination (authors' unpublished data). The relatively high number of seronegative individuals in our twice-vaccinated study group may be partly explained by the fact that the Enzygnost Anti-Parotitis-Virus/IgG test we used has been shown to overestimate seronegativity [26]. At present, it is not known what serum levels of antibody to mumps virus are protective.

Waning immunity due to the lack of natural booster infections may increase the proportion of antibody-negative individuals in countries that have succeeded in eliminating indigenous mumps via an extensive vaccination program. This could eventually enable the reemergence of subclinical or clinical mumps, as has been predicted to occur with measles [27]. A mathematical model of the persistence of measles virus-specific humoral immunity predicts that vaccine-induced immunity has a mean duration of 25 years in the absence of reexposure [11]. It is, however, also possible that some individuals become susceptible to a subclinical infection relatively soon after vaccination [28], complicating the mathematical modeling. The latter situation may be relevant for vaccine-induced immunity to mumps virus, because the seroconversion rate for mumps vaccination is lower than the seroconversion rate for measles vaccination. A good example of the difficulties in eliminating mumps virus infection, even when vaccination coverage is high, is the recent mumps epidemic in the United States [6, 29]: the majority of those who became infected had been vaccinated with 2 doses of MMR vaccine, thus raising a severe concern regarding the efficacy of the vaccine as well as the question of why the vaccine failed [29].

Although natural infection with mumps virus seems to lead to higher antibody levels and better persistence of detectable anti-mumps virus IgG antibodies than does vaccination, our results show that a similar trend may not be observed for cellular immunity. Therefore, although waning of humoral immunity to mumps virus is also significant in individuals vaccinated twice with MMR vaccine, it does not necessarily mean that these individuals become unprotected, given that the vaccine-induced mumps antigen-specific cellular immune responses seem to last longer than do measurable humoral immunity. An indication of a possible protective role for cellular immunity is evident in individuals who do not have detectable mumps virus-specific antibodies after vaccination but who still do not contract mumps virus infection even after heavy exposure to those with natural disease [30]. In the present study, PBMCs from the subjects who no longer had measurable mumps virus-specific antibodies still showed prominent lymphoproliferative responses and significant cytokine production when stimulated with mumps antigen. Further studies are needed to confirm whether cellular immunity alone can provide protection against mumps virus infection.

Current vaccination schemes are believed to provide sufficient herd immunity to keep mumps virus epidemics under control, but when circulating virus disappears and natural booster infections no longer occur, the situation may change. Therefore, procuring detailed information on the persistence of vaccine-induced immunity to mumps virus is of vital importance. However, none of the current parameters have been reliably analyzed for their correlation with protection from disease in circumstances in which an outbreak emerges after a long mumps-free period.

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Acknowledgments

We thank Prof. Pauli Leinikki for the valuable help in the revision of the manuscript and Dr. Valma Harjutsalo for the statistical analysis of our data.

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Footnotes

  • Potential conflicts of interest: none reported.

  • Financial support: National Public Health Institute (Finland).

  • Received January 12, 2007.
  • Accepted April 2, 2007.
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References

  1. ↵
    1. Peltola H,
    2. Heinonen OP,
    3. Valle M,
    4. et al
    . The elimination of indigenous measles, mumps, and rubella from Finland by a 12-year, two-dose vaccination program. N Engl J Med 1994;331:1397-402.
    CrossRefMedlineWeb of Science
  2. ↵
    1. Peltola H,
    2. Davidkin I,
    3. Paunio M,
    4. Valle M,
    5. Leinikki P,
    6. Heinonen OP
    . Mumps and rubella eliminated from Finland. JAMA 2000;284:2643-7.
    Abstract/FREE Full Text
  3. ↵
    1. Plotkin SA,
    2. Orenstein WA
    1. Plotkin SA,
    2. Wharton M
    . Mumps vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 3rd ed. Vol. 284. Philadelphia: W.B. Saunders; 1999. p. 267-92.
  4. ↵
    1. Zuckerman A,
    2. Banatvala J,
    3. Pattison J,
    4. Griffiths P,
    5. Schoub B
    1. Leinikki P
    . Mumps. In: Zuckerman A, Banatvala J, Pattison J, Griffiths P, Schoub B, editors. Principles and practice of clinical virology. 5th ed. Chichester, UK: John Wiley & Sons; 2004. p. 459-66.
  5. ↵
    1. Nokes D,
    2. Anderson R
    . Measles, mumps and rubella vaccine: what coverage to block transmission? Lancet 1988;2:1374.
    MedlineWeb of Science
  6. ↵
    Centers for Disease Control and Prevention. Update: multistate out-break of mumps—United States, January 1–May 2, 2006. MMWR 2006;55:559-63.
    Medline
  7. ↵
    1. Gut J-P,
    2. Lablache C,
    3. Behr S,
    4. Kirn A
    . Symptomatic mumps virus reinfections. J Med Virol 1995;45:17-23.
    MedlineWeb of Science
  8. ↵
    1. Crowley B,
    2. Afzal M
    . Mumps virus reinfection—clinical findings and serological vagaries. Commun Dis Public Health 2002;5:311-3.
    Medline
  9. ↵
    1. Davidkin I,
    2. Jokinen S,
    3. Paananen A,
    4. Leinikki P,
    5. Peltola H
    . Etiology of mumps-like illnesses in children and adolescents vaccinated for measles, mumps, and rubella. J Infect Dis 2005;191:719-23.
    Abstract/FREE Full Text
  10. ↵
    1. Davidkin I,
    2. Valle M,
    3. Julkunen I
    . Persistence of anti-mumps virus antibodies after a two-dose MMR vaccination: a nine-year follow-up. Vaccine 1995;13:1617-22.
    CrossRefMedlineWeb of Science
  11. ↵
    1. Mossong J,
    2. Nokes DJ,
    3. Edmunds WJ,
    4. Cox MJ,
    5. Ratnam S,
    6. Muller CP
    . Modeling the impact of subclinical measles transmission in vaccinated populations with waning immunity. Am J Epidemiol 1999;150:1238-49.
    Abstract/FREE Full Text
  12. ↵
    1. Gans H,
    2. Yasukawa L,
    3. Rinki M,
    4. et al
    . Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months. J Infect Dis 2001;184:817-26.
    Abstract/FREE Full Text
  13. ↵
    1. Good RA,
    2. Zak SJ
    . Disturbances in gamma globulin synthesis as “experiments of nature.”. Pediatrics 1956;18:109-49.
    Abstract/FREE Full Text
  14. ↵
    1. Dhiman N,
    2. Ovsyannikova IG,
    3. Jacobson RM,
    4. et al
    . Correlates of lymphoproliferative responses to measles, mumps, and rubella (MMR) virus vaccines following MMR-II vaccination in healthy children. Clin Immunol 2005;115:154-61.
    CrossRefMedlineWeb of Science
    1. Broliden K,
    2. Abreu ER,
    3. Arneborn M,
    4. Bottiger M
    . Immunity to mumps before and after MMR vaccination at 12 years of age in the first generation offered the two-dose immunization programme. Vaccine 1998;16:323-7.
    CrossRefMedlineWeb of Science
    1. Johnson CE,
    2. Kumar ML,
    3. Whitwell JK,
    4. et al
    . Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. eleven to thirteen years. Pediatr Infect Dis J 1996;15:687-92.
    CrossRefMedlineWeb of Science
  17. ↵
    1. Nakayama T,
    2. Urano T,
    3. Osano M,
    4. et al
    . Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response. Microbiol Immunol 1990;34:497-508.
    MedlineWeb of Science
  18. ↵
    1. Peltola H,
    2. Karanko V,
    3. Kurki T,
    4. et al
    . Rapid effect on endemic measles, mumps, and rubella of nationwide vaccination programme in Finland. Lancet 1986;1:137-9.
    MedlineWeb of Science
  19. ↵
    1. Julkunen I,
    2. Hautanen A,
    3. Keski-Oja J
    . Interaction of viral envelope glycoproteins with fibronectin. Infect Immun 1983;40:876-81.
    Abstract/FREE Full Text
  20. ↵
    1. Gans HA,
    2. Maldonado Y,
    3. Yasukawa LL,
    4. et al
    . IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants. J Immunol 1999;162:5569-75.
    Abstract/FREE Full Text
  21. ↵
    1. Thomson AW,
    2. Lotze MT
    1. Ding Y,
    2. Fu S,
    3. Zamarin D,
    4. Bromberg J
    . Interleukin-10. In: Thomson AW, Lotze MT, editors. The cytokine handbook. 4th ed. Vol. 1. London: Academic Press; 2003. p. 603-25.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Usonis V,
    2. Bakasenas V,
    3. Kaufhold A,
    4. Chitour K,
    5. Clemens R
    . Reactogenicity and immunogenicity of a new live attenuated combined measles, mumps and rubella vaccine in healthy children. Pediatr Infect Dis J 1999;18:42-8.
    CrossRefMedlineWeb of Science
    1. Feiterna-Sperling C,
    2. Brönnimann R,
    3. Tischer A,
    4. Stettler P,
    5. Durrer P,
    6. Gaedicke G
    . Open randomized trial comparing the immunogenicity and safety of a new measles-mumps-rubella vaccine and a licensed vaccine in 12- to 24-month-old children. Pediatr Infect Dis J 2005;24:1083-8.
    CrossRefMedlineWeb of Science
  24. ↵
    1. Cruz Rojo C,
    2. Rodríguez Iglesias M,
    3. Olvera J,
    4. álvarez Girón M
    . Study of the immune response engendered by different combined measles, mumps and rubella (MMR) vaccines in an area of Andalusia (Spain). Vaccine 2003;22:280-6.
    CrossRefMedlineWeb of Science
  25. ↵
    1. Christenson B,
    2. Böttiger M
    . Methods for screening the naturally acquired and vaccine-induced immunity to the mumps virus. Biologicals 1990;18:213-9.
    CrossRefMedlineWeb of Science
  26. ↵
    1. Backhouse J,
    2. Gidding H,
    3. McIntyre P,
    4. Gilbert G
    . Evaluation of two enzyme immunoassays for detection of immunoglobulin G antibodies to mumps virus. Clin Vaccine Immunol 2006;13:764-7.
    Abstract/FREE Full Text
  27. ↵
    1. Mossong J,
    2. Muller CP
    . Modelling measles re-emergence as a result of waning of immunity in vaccinated populations. Vaccine 2003;21:4597-603.
    CrossRefMedlineWeb of Science
  28. ↵
    1. Glass K,
    2. Grenfell BT
    . Antibody dynamics in childhood diseases: waning and boosting of immunity and the impact of vaccination. J Theor Biol 2003;221:121-31.
    CrossRefMedlineWeb of Science
  29. ↵
    1. Kancherla VS,
    2. Hanson IC
    . Mumps resurgence in the United States. J Allergy Clin Immunol 2006;118:938-41.
    CrossRefMedlineWeb of Science
  30. ↵
    1. Weibel R,
    2. Stokes J Jr,
    3. Buynak E,
    4. Whitman J Jr,
    5. Hilleman M
    . Live, attenuated mumps-virus vaccine 3: clinical and serologic aspects in a field evaluation. N Engl J Med 1967;276:245-51.
    Medline
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  1. J Infect Dis. (2007) 196 (6): 861-867. doi: 10.1086/521029
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