Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine

Abstract

BackgroundRecent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure.MethodsSera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18–28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels.ResultsThere were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year post-MMR3, mumps antibody declined toward baseline but remained elevated (P < .05). The correlation between PRN titers and ELISA measurements was poor (r2 = .49), although sera with the highest amount of HN IgG also had the highest PRN titers.ConclusionsIndividuals with the lowest baseline PRN titers had the largest increase in frequency of samples that became positive for HN and NP by ELISA. A third dose of MMR may benefit certain individuals with a low level of mumps virus–neutralizing antibody, especially in the context of an outbreak or other high-risk setting. Additionally, poor correlation among serologic tests does not allow effective prediction of PRN titer by ELISA.

Seroprevalence and Determinants Associated with Mumps Antibodies after 20 Years of MMR Vaccination in Urban Area of Shanghai, China

“…Three epidemiologic studies conducted in schools and a university, suggested effectiveness of using MMR3 as public health intervention for mumps outbreak control [ 20 , 21 , 22 ]. Two immunogenicity studies administered MMR3 to subjects aged 18-28 years, demonstrated a significant increase in mumps antibodies one month after vaccination; however antibody titers returned to near-baseline levels a year later [ 23 , 24 ]. In light of the available evidence, a third dose of mumps containing vaccine is recommended in the US only to persons at increased risk for acquiring mumps because of an outbreak [ 25 ].…”

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood

“…Similar to our finding of a 6-foldlower antibody titer to the genotype G strain, Rubin et al (26) reported that titers to the genotype G strain in a 2006 mumps outbreak were half those of the Jeryl Lynn strain. Administration of a third MMR dose temporarily boosted antibody titers, but they returned to near-baseline after 1 y (55,57). Epidemiological evidence suggests that a third dose of MMR may have a protective role in outbreak settings (23,54,57).…”

“…Administration of a third MMR dose temporarily boosted antibody titers, but they returned to near-baseline after 1 y (55,57). Epidemiological evidence suggests that a third dose of MMR may have a protective role in outbreak settings (23,54,57). Adding a routine third dose to the current vaccine schedule is feasible to implement (when combined with meningococcal vaccine at age 16), but it does not lead to a sustained increase in antibody responses (57).…”

“…Epidemiological evidence suggests that a third dose of MMR may have a protective role in outbreak settings (23,54,57). Adding a routine third dose to the current vaccine schedule is feasible to implement (when combined with meningococcal vaccine at age 16), but it does not lead to a sustained increase in antibody responses (57). It is possible that a third-dose booster with a different genotype (i.e., genotype G) may lead to sustained cross-genotype immunity, but this would require considerable research to demonstrate safety and short-and long-term effectiveness.…”

The Human CD4+T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope

“…Antibodies directed against HN have been demonstrated to play a major role in neutralization of the virus (6–8). However, antibody concentrations against HN were relatively low or below detection levels after MuV infection or vaccination (9, 10). Interestingly, a large fraction of the mumps-specific antibodies is directed against N and can be detected in almost all individuals after vaccination (9–11).…”