Two doses of measles-mumps-rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity and two-dose vaccine failures occur.
We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year.
[R]esponse was minimal post-MMR3.
MeV [measles virus] IgG avidity results did not correlate with neutralization results.
[R]esults showed minimal qualitative improvements in immune response post-MMR3.
We did not find compelling data to support a routine third dose of MMR vaccine.
Two doses of MMR vaccine are generally sufficient to provide long-lasting protection against measles. Nonetheless… third doses have been administered during mumps outbreaks among highly vaccinated populations and in non-outbreak settings among healthcare personnel, military recruits, international travelers, and college students who may have been two-dose vaccinated but lacked documentation.
The immunogenicity of the MeV component of a third MMR dose has not been studied.
[S]ubjects were offered a third dose of MMR vaccine. Serum was collected from all subjects immediately before (baseline), and one month and one year after MMR3.
MeV IgG antibody avidity was evaluated to determine whether there was a correlation between neutralizing antibody concentrations and strength of antibody binding [avidity].
Of 662 subjects at baseline… 301 (45.5%) had high [MeV neutralizing antibody] concentrations.
Of 23 subjects with low baseline antibody concentrations… One year post-MMR3… [zero] had high MeV neutralizing antibody concentrations.
Overall, at 1-month post-MMR3… 399 (60.3%) had high neutralizing antibody concentrations.
One year post-MMR3… 308 (49.9%) had high neutralizing antibody concentrations.
[A]lmost all subjects were MeV seropositive prior to receiving MMR3, and subjects’ antibody levels returned to near-baseline 1-year post-vaccination.
[W]e did not find compelling qualitative data to support a routine third dose of MMR vaccine.
Although 95% of vaccinated persons have detectable MeV antibodies 10-15 years after the second MMR dose, waning immunity occurs after two doses, and two-dose failures have been documented.
Most subjects did not have a positive CMI [T-cell mediated immunity] result at baseline, despite the majority of subjects having medium or high baseline MeV antibody concentrations. [T]his was not greatly boosted by MMR3.
[W]e found mixed results at 1-month post-MMR3 with no correlation between MeV antibody response and MeV T-cell response.
Typically, IgG avidity maturation for measles shifts from low to high 4 months following immunization or infection which might negate additional increases in antibody avidity with subsequent doses of measles-containing vaccine.
Overall, MeV neutralizing antibody concentrations initially increased after MMR3 but declined to near-baseline levels one year later. Although our findings showed that MMR3 increased antibody levels for the small percentage of subjects with low MeV neutralizing antibody concentration levels who were on the cusp of protection, the CMI and avidity results in the subset tested showed that MMR3 did not result in substantial improvements in the quality of the immune response.
[A third dose of MMR] is unlikely to solve the problem of waning immunity in the U.S.