Is a third dose of the Measles, Mumps, and Rubella (MMR) vaccine ever necessary?

Third Dose of MMR Vaccine: Clinical Indications

Yes, a third dose of MMR vaccine is indicated specifically during mumps outbreaks for persons identified by public health authorities as being at increased risk for acquiring mumps. 1

Primary Indication: Mumps Outbreak Settings

During mumps outbreaks, a third dose of MMR is recommended for persons previously vaccinated with 2 doses who are identified by public health authorities as part of a group or population at increased risk for acquiring mumps because of an outbreak. 1, 2, 3

• This recommendation was formally adopted by the Advisory Committee on Immunization Practices (ACIP) in October 2017 to address the substantial increase in mumps outbreaks occurring in the United States since late 2015. 3
• The purpose is to improve protection against mumps disease and mumps-related complications in outbreak settings. 3
• ACIP determined that a third dose of MMR vaccine is both safe and effective at preventing mumps. 3

Evidence Supporting Third Dose Efficacy

Research demonstrates that MMR3 produces modest but statistically significant increases in mumps antibody levels, with benefits particularly pronounced in individuals with low baseline antibody titers. 4

• At 1 month post-MMR3, mumps antibody levels increase significantly by ELISA and plaque reduction neutralization (PRN) assays. 4
• At 1 year post-MMR3, mumps antibody levels decline toward baseline but remain elevated above pre-vaccination levels. 4
• Individuals with the lowest baseline PRN titers experience the largest increases in antibody response. 4

Safety Profile of Third Dose

The third dose of MMR is safe and well-tolerated, with only mild and transient adverse events reported. 5

• In a study of 662 young adults receiving MMR3, approximately 18% reported more symptoms after vaccination than at baseline. 5
• The most common symptoms were headache (13%), joint problems (10%), diarrhea (8%), and lymphadenopathy (6%), with median onset at days 3-6 and median duration of 1-2 days. 5
• Injection-site symptoms occurred in 25% of participants with median duration of 1-2 days. 5
• Only one healthcare visit for a potential vaccination-related symptom (urticaria) was reported. 5

Situations Where Third Dose Is NOT Routinely Indicated

For routine vaccination outside of outbreak settings, only 2 doses of MMR are recommended (first dose at 12-15 months, second dose at 4-6 years). 1, 2

• The standard 2-dose schedule provides long-lasting immunity in at least 95% of recipients. 1
• A third dose is not part of routine catch-up vaccination schedules. 1

Special Considerations for Seronegative Individuals

While a third dose may be administered to individuals found to be seronegative after 2 documented MMR doses, this represents a small minority (approximately 3.7% in one study). 6

• Research identified 4 of 109 participants (3.67%) who were seronegative for rubella-specific antibodies despite 2 prior MMR doses. 6
• Following a third dose, no participants remained seronegative, and approximately one-third experienced a significant boost (≥4-fold) in antibody titers. 6

Clinical Algorithm for Third Dose Decision

Administer a third dose of MMR if:

• Public health authorities have declared a mumps outbreak AND the patient is identified as being at increased risk (e.g., college students, healthcare workers in affected facilities). 1, 3

Do NOT routinely administer a third dose if:

• The patient has completed the standard 2-dose series and is not in an outbreak setting. 1, 2
• The patient requires measles or rubella protection only (mumps outbreak is the sole indication for third dose). 1

Important Caveats

• The third dose recommendation is specific to mumps outbreak control and does not apply to measles or rubella outbreak settings, where standard 2-dose vaccination remains the recommendation. 1
• For measles postexposure prophylaxis, only 1 dose of MMR within 72 hours is recommended for unvaccinated persons, followed by completion of the 2-dose series. 1
• Both M-M-R II and PRIORIX vaccines are fully interchangeable for all indications, including the third dose during mumps outbreaks. 1