What does it mean if a patient is measles Immunoglobulin G (IgG) positive but mumps IgG negative after receiving the Measles, Mumps, and Rubella (MMR) vaccine?

Understanding Discordant MMR Serology Results

A measles IgG-positive but mumps IgG-negative result after MMR vaccination is common and occurs because the mumps component of MMR vaccine generates weaker and less durable antibody responses compared to measles, with studies showing mumps seronegativity rates of 23-29% even in vaccinated populations.

Why This Happens: Differential Immune Responses to MMR Components

The three components of MMR vaccine do not generate equal immune responses:

• Measles component produces the strongest and most durable antibody response, with seroconversion rates of approximately 94-96% after vaccination 1, 2
• Mumps component generates significantly weaker immunity, with 23-29% of vaccinated individuals showing seronegativity or levels below protective thresholds 1, 2
• Rubella component produces intermediate but generally robust responses, with the lowest seronegativity rates (approximately 4-8%) 1, 2

Research demonstrates that mumps-specific IgG concentrations are significantly lower than rubella IgG, and mumps-specific memory B cells are 5-10 times less frequent than measles or rubella memory B cells 3. Approximately 10% of vaccinated individuals have no detectable memory B cells to mumps at all 3.

Common Mechanisms for Discordant Results

Primary Vaccine Failure

• Studies show that 19.5% of children have measles antibody below protective levels and 23.4% have inadequate mumps antibody 2-4 years after first MMR dose 1
• Only 4.6% show inadequate rubella antibody during the same timeframe 1
• This explains why someone can be positive for one component but negative for another—each antigen has different immunogenicity 1

Waning Immunity

• Mumps antibody levels decline more rapidly than measles or rubella antibodies over time 3
• Young adults who received MMR in childhood show disproportionately low mumps immunity compared to measles and rubella, even when vaccinated appropriately 3
• This differential waning explains mumps outbreaks in highly vaccinated college populations 3

Interference from Immune Globulin or Maternal Antibodies

• If MMR was given within 14 days of receiving immune globulin products, vaccine-induced immunity may be compromised for all three components, but mumps is most vulnerable 4
• The interval between IG administration and vaccination affects each component differently 4

Age at First Vaccination

• Children vaccinated at 12 months have significantly higher measles seronegativity rates than those vaccinated at 13-17 months 1
• This age effect may differentially impact individual components 1

Clinical Implications

For This Patient

• The patient should receive a second dose of MMR vaccine if they have not already received two doses 1, 2
• After a second MMR dose, the proportion negative to one or more antigens drops to less than 4% 1
• Studies from Kuwait and other populations support considering a third MMR dose for those with persistent mumps seronegativity, though U.S. guidelines do not routinely recommend this 2

Important Caveats

• Serologic testing does not perfectly correlate with protection—some individuals with low or negative antibody titers may still have cellular immunity and be protected 1, 5
• IgG avidity testing and memory B cell assays provide better assessment of immune quality but are not routinely available 3, 5
• The lack of correlation between seropositivity to different MMR antigens (except for a small 1% who are negative to all three) confirms that immune responses to each component are independent 1

Outbreak Context

• During mumps outbreaks, individuals with documented two-dose MMR vaccination history may still benefit from a third dose, regardless of serologic status 2
• Mumps outbreaks occur even in highly vaccinated populations due to both waning immunity and antigenic mismatch between vaccine strain (Jeryl Lynn, genotype A) and circulating wild-type strains (predominantly genotype G) 3

What NOT to Do

• Do not assume that because someone received MMR vaccine, they are equally protected against all three diseases 1, 3
• Do not delay a second MMR dose based on positive serology to one component—the vaccine is safe and may boost responses to all antigens 1
• Do not use total IgG antibody levels alone as the sole measure of protection in highly vaccinated populations, as they may not accurately reflect functional immunity 1