MMR Vaccine

Mechanism of Action

The MMR vaccine is a live attenuated combination vaccine formulated with live attenuated viruses, making it a harmless, less-virulent version of the infectious agents from which it provides protection. The MMR vaccine stimulates the immune system to protect against measles, mumps, and rubella. Due to its live attenuated nature, the MMR vaccine demonstrates high efficacy but necessitates multiple doses for complete immunity to be attained.[3] Furthermore, this vaccine is recommended for specific patient populations as post-exposure prophylaxis.

The 3 live attenuated viruses in the new MMR vaccine are genetically similar to the corresponding components of the existing MMR vaccine. Humoral immunity is evaluated from the clinical data of 13 randomized controlled trials, and the serologic response thresholds were achieved for all antigens. The Advisory Committee on Immunization Practices (ACIP) has determined the newly approved MMR vaccine to be immunogenic and safe.[6]

Administration

Estimates of the effectiveness of the MMR vaccine are 99% in measles prevention after a second vaccination, over 95% in the prevention of mumps, and 90% in the prevention of rubella after a single dose. ACIP suggests that vaccine doses in a series should arrive from the same manufacturer; however, vaccination should not be delayed if the vaccine from the same manufacturer is unavailable. Clinical trials have demonstrated that the new MMR vaccine is safe and efficacious when administered as a second dose.[7][8]

• The first dose should be administered to individuals aged 12 to 15 months, and the second dose should be administered between ages 4 and 6. The second dose is preferably administered before kindergarten or school entry. Note that the interval between doses should not be shorter than 28 days.[6]

• The vaccine can be given in 2 doses to individuals aged 12 months to 13 years for unimmunized children and adolescents.

• For unimmunized adults born after 1970, 1 dose should be given unless they are traveling outside North America, working in health care, students in post-secondary educational settings, or military personnel.

• For unimmunized adults born before 1970, 1 dose should be given if they are students in post-secondary educational settings or traveling outside North America and 2 doses if they work in health care or are military personnel.

• The recommendation is to give the first and/or second dose of MMR in advance to children who live or travel in areas with an outbreak of measles (defined as at least 3 cases with a temporal and spatial relationship) and children traveling outside US borders. In the specified situations, the initial dose of MMR should be administered between 6 and 11 months of age, followed by subsequent vaccinations according to the recommended schedule—2 doses of vaccine, with an interval of at least 28 days apart, typically administered between 12 and 15 months of age.[3]

• In the case of measles outbreaks, a vaccine can be given to infants aged 6 months. Then vaccinations can be continued according to a generally accepted schedule (2 doses in 13 to 14 months and 10 years, respectively).

• Children aged between 12 and 23 months should receive the MMR vaccine and a univalent varicella vaccine at the same visit instead of the MMRV vaccine to reduce the risk of fever and febrile seizures. The risk is estimated to be around 1 additional febrile seizure per 2300 to 2800 doses of MMRV vaccine in this patient cohort.[3]

• Patients with laboratory confirmation of measles, mumps, or rubella immunity are considered immune to this disease, and no need for immunization vaccination exists. In practice, however, 2 doses of the MMR vaccine are also given in this situation, which is dictated by the lack of availability of monovalent vaccines against these viruses.[3] Seronegative patients who have proof of adequate immunization do not require further vaccination.

Specific Patient Populations

Hepatic impairment: No dose adjustment is provided in the vaccine labeling. Expert opinion is that MMR vaccines should be administered early in chronic liver disease for effective immune response. The American Society of Transplantation Infectious Diseases Community of Practice suggests that children should be vaccinated before liver transplantation.[9]

Renal impairment: No dose adjustment is provided.

Pregnancy considerations: Pregnant women who have not been vaccinated and have laboratory-confirmed measles disease should receive intravenous (IV) immunoglobulin after exposure. Measles in pregnant women may have a more severe course and serious complications.[3]

Breastfeeding considerations: The CDC states that the MMR vaccine administered to mothers during lactation does not affect the safety of infants or mothers. The rubella vaccine virus can be secreted in breast milk. The rubella virus is attenuated and generally does not infect the infant. However, transmission and mild clinical infection are possible. No definitive evidence suggests the presence of live attenuated mumps or measles vaccine virus in the breast milk. Additionally, the absence of exclusive breastfeeding until 5 months of age can result in poor response to measles vaccination.[4]

Pediatric patients: The efficacy and safety of the MMR vaccine in infants 12 months or younger are inconclusive. ACIP recommends 2 doses of MMR vaccine administered ≥28 days apart for catch-up immunization of previously unvaccinated children.[6]

Older patients: Clinical studies of MMR vaccines have not evaluated patients aged 65 or younger if they respond differently from younger individuals.

Post-Exposure Prophylaxis

Immunoglobulin (400 mg/kg) can be administered 6 days after exposure. The intent is to prevent or reduce the severity of measles, but it is not given to immunocompetent persons who have received 1 dose of MMR after 12 months of age. This post-exposure prophylaxis is only for patients exposed to measles who have an increased risk of complications and are contraindicated to MMR vaccination. This group includes patients:

• Severe immunodeficiency, regardless of immune status or immunization

• After a bone marrow transplant, up to at least 12 months after the end of immunosuppressive therapy or longer if there is a graft-versus-host reaction

• Treated for acute lymphoblastic leukemia until at least 6 months after completing immunosuppressive chemotherapy

• Infected with HIV and a percentage of CD4 cells less than 15% (all age groups) or CD4 cell counts below 200 cells/mm³ (aged 5 and older). They have not received the MMR vaccine after effective antiretroviral therapy.

Newborn babies and infants aged up to 6 months should receive immunoglobulin intramuscularly (IGIM) at a dose of 0.5 mL/kg (maximum dose 15 mL) or intravenous immunoglobulin (IVIG) 400 mg/kg within 6 days of exposure.

Infants aged 6 to 12 months may receive the MMR vaccine within 72 hours of exposure or IGIM at 0.5 mL/kg (maximum dose of 15 mL) or IVIG 400 mg/kg within 6 days of exposure.

For children aged at least 12 months, the MMR vaccination is preferred to IGIM or IVIG.

After exposure, children with contraindications for MMR vaccination should receive IVIG 400 mg/kg instead of IGIM.[1]

Adverse Effects

The adverse effects associated with vaccines are listed below.

MMR Vaccine

Adverse events tend to occur with the first dose. 1 to 3 weeks following vaccination, 5% of immunized children experience malaise and fever, which can present with or without a rash that lasts up to 3 days.[2]

MMRV Vaccine

Ten percent or more of vaccine recipients experience redness and pain at the injection site or a fever of 39 °C or less. Less than 1% to 10% of patients experience a measles-like, rubella-like, or varicella-like rash in addition to swelling and a fever greater than 39 °C.[5][10]

Rubella-Containing Vaccines

Patients receiving rubella-containing vaccines may experience acute transient arthritis or arthralgia 1 to 3 weeks after immunization. These symptoms last 1 to 3 weeks and rarely recur. These symptoms are more common in post-pubertal females, who develop arthralgia in 25% of cases and arthritis in 10% of patients after immunization. No evidence of an increased risk of new-onset chronic arthropathies exists.[5]

Immune Thrombocytopenic Purpura

A rare adverse reaction to the MMR or MMRV vaccine is immune thrombocytopenic purpura, which may occur within 6 weeks of immunization. In most children, immune thrombocytopenic purpura resolves within 3 months without complication. In these cases, serologic status can undergo an evaluation to determine the need for an additional dose. Clinicians should consider the risks of another adverse event of immune thrombocytopenic purpura before a second dose of the vaccine is required.[11]

Encephalitis

Encephalitis occurs in approximately 1 per million doses, compared to 1 in 1000 with infection with the measles virus. Measles encephalitis is due to disseminated measles vaccine virus infection. The neuropathological examination reveals inclusion-body encephalitis.[12]

Febrile Seizures

Children between the ages of 12 and 23 months should receive the MMR vaccine and a univalent varicella vaccine at the same visit instead of an MMRV vaccine to reduce the risk of fever and febrile seizures. The incidence of febrile seizures is highest after the first MMR dose.[13] The risk is estimated to be around 1 additional febrile seizure per 2300 to 2800 doses of MMRV vaccine in this patient cohort.[14][15]

Allergies

The trace amount of egg or chicken protein in the MMR and MMRV vaccine is insufficient to cause an allergic reaction in those who are egg-allergic. Recently approved MMR vaccine does not contain gelatin.[16]

Contraindications

Booster doses with a measles-containing vaccine after appropriate vaccination is not necessary.

Contraindications of Vaccines

• Severe allergic reaction/anaphylaxis after a previous dose of MMR/MMRV or after one of the components of the vaccine, such as neomycin and gelatin.[5]

• Pregnancy or planning should be discouraged within 28 days of vaccination due to the risk of congenital rubella. However, performing a pre-vaccination pregnancy test is unnecessary if the patient denies pregnancy. 

• Immunodeficiency

• Hematopoietic proliferative diseases

• Solid tumors or chemotherapy 

• Congenital immunodeficiency disorders

• Long-term immunosuppressive treatment, when administering high doses of steroids, which is at least 2 mg/kg/d or at least 20 mg/d prednisone equivalents for persons over 10 kg for more than 14 consecutive days, MMR vaccination should be postponed a month. However, lower systemic corticosteroids, supporting physiological doses (the so-called replacement therapy), and local corticosteroid injections (eg, into joints or tendons) are not contraindications to MMR vaccination.

• HIV infection and severe immunosuppression is defined as the percentage of CD4+ lymphocytes (CD4) less than 15% at any age. In case the percentage of CD4 is not available, the threshold values are as follows: CD4 less than 750/mL for children aged 12 months; CD4 below 500/mL for children aged 1 to 5; CD4 less than 200/mL for children aged 5 and older. 

• Family history for congenital or hereditary immunodeficiency in parents or siblings, except for persons whose immunological system is confirmed by laboratory tests.[5]

Relative Contraindications

• Treatment in the last 11 months with blood products or immunoglobulins may contain antibodies or inhibit the host response to a live vaccine. Therefore, the recommended interval for such treatment to MMR vaccination is from 3 to 11 months, depending on the type of transfused preparation. 

• Anamnesis with thrombocytopenia or thrombocytopenia may show an increased risk of clinically significant thrombocytopenia after immunization with MMR or MMRV. Therefore, decisions on the first dose of MMR for children with a thrombocytopenia history must consider the risks and benefits. In general, the benefits outweigh the risks. Factors to be evaluated when making this decision include:
  • Relapse of thrombocytopenia after MMR in patients with a history of thrombocytopenia (related and unrelated to the vaccine).
  • Probability of the child's exposure to measles, mumps, and rubella (eg, planned trips abroad, the epidemiology in the place of residence or stay of the child).

• Before the second dose of MMR vaccination, clinicians can perform serological tests to determine the necessity. Children with a protective level of measles, mumps, and rubella antibodies do not need a second dose. However, for children with a history of thrombocytopenia who do not have a protective level of measles, mumps, or rubella antibodies, decisions on administering a second dose of MMR are assessed individually for the risks and benefits.

• Acute moderate or severe disease, with or without fever, to avoid the imposition of any vaccine reaction, symptoms of infection, and the vaccine burden with symptoms due to infection. Vaccinate children with mild infections (eg, upper respiratory tract infection, ear infection, diarrhea). Postponing vaccination in such a situation unnecessarily delays the implementation of the immunization program and lengthens the susceptibility to infection.[5]

Contraindications Do Not Constitute

• A positive tuberculin test in people with active TB infection before vaccination. A simultaneous tuberculin test should be performed either on the day of MMR vaccination or 4 to 6 weeks after because the measles virus in the vaccine may weaken the skin reaction to tuberculin. 

• Breastfeeding period

• Pregnancy of the mother of a child who is to receive a vaccine or pregnancy in a person near the child

• Reproductive period

• A person who is immunocompromised in the family or immediate environment

• Asymptomatic HIV infection or HIV infection with mild symptoms, without immune disorders

• Allergy to egg protein in children with a history of mild allergy to a hen egg, the risk of anaphylactic reaction after MMR vaccination is the same as in the general population.[5] 

• In children with severe allergies - anaphylaxis or an immediate reaction after ingestion. Allergy to egg protein is automatically included in the group at higher risk of sudden allergic reactions after vaccines. In the case of MMR, gelatin and neomycin are more allergenic to egg protein.[14][15]

Monitoring

Monitor for seizures and anaphylaxis following administration.[17]

Toxicity

Limited data are available regarding the safety of administering an additional dose of the MMR vaccine. The administration of an additional dose of a vaccine may be necessary in cases where there is uncertainty about a person's vaccination history or due to programmatic errors, such as vaccination mistakes. Among 5067 reported instances of excess vaccine doses administered between 2007 and 2017, three-fourths of cases did not result in adverse events following immunization (AEFI). The most commonly reported adverse health events were pyrexia (12.8%), injection site erythema (9.7%), injection site pain (8.9%), and headache (6.6%). The percentage of adverse health events among these cases was comparable to all cases submitted to the Vaccine Adverse Event Reporting System (VAERS) during the same study period.[18]

Enhancing Healthcare Team Outcomes

Vaccination with the MMR vaccine requires an interprofessional approach as the proper administration of the vaccine changes according to the patient population and the clinical scenario. The mumps outbreaks have increased in the US since 2006. Due to the resurgence of mumps and the risk associated with rubella and measles, increasing MMR coverage is necessary. The availability of MMR vaccines from different manufacturers ensures the continuous supply of vaccines.[6][19]

Vaccination of children with neurological diseases should follow accepted rules and vaccination schedules. One should remember that the risk of severe infection, the need for hospitalization, and complications in children with chronic disease are significantly higher than in the healthy population. Also, each infection causes a break in rehabilitation, adversely affecting the child's neurological status. Also, children with chronic diseases are more likely to be in healthcare facilities, increasing infection risk.

Contraindications to MMR vaccination in children with neurological diseases are limited and temporary.[5] They include the following:

• Undetermined neurological diagnosis

• Suspicion of progressive central nervous system disease with epilepsy

• Six months after the last convulsion seizure

• Unstabilized neurological condition

Contraindications to MMR vaccination do not constitute:

• Epilepsy with an excellent response to treatment (at least 6 months without seizures)

• A neurological disorder before the start of vaccination

In children with epilepsy, the recommendation is to administer antipyretic drugs for 6 to 12 days after administration of MMR - fever that may occur as an adverse reaction may trigger seizures.[2][3]

Another recommendation is to educate patients with a multi-disciplinary team about vaccination's perceived but false risks. For example, the association of MMR with autism spectrum disorder (ASD) has aroused much controversy in recent years. Several antivaccine advocacy groups put the hypothesis linking autism and inflammatory bowel disease with MMR vaccination forward in the last century.[20]

In 1998, Lancet published an article where researchers reported a link between the MMR vaccine and intestinal leukemia. The article's basis was the temporal relationship between the increase in ASD diagnoses (observed since the 1980s) and the rise in recommended childhood vaccines - against haemophilus influenzae type B, hepatitis B, chickenpox, pneumococci, influenza, and MMR vaccine.[20][21]

The thesis put forward by Wakefield's team is the starting point for many epidemiological and prospective studies worldwide that have ruled out a cause-and-effect relationship between vaccination (including MMR) and the occurrence of ASD or inflammatory bowel disease. Subsequent analysis proved that increased ASD diagnoses resulted from changes in ASD recognition criteria as a neurodevelopmental disorder and increasing awareness of this problem.

Prospective studies have shown that ASD symptoms often occur in the first year of life, before the first dose of MMR. In 2004, the journalist revealed that Wakefield's test was conducted in a manner that did not follow medical ethics and was inaccurate. Most of the study's authors officially withdrew unreliable applications, and the Lancet completely retracted the article in 2010.[22] However, if adverse events occur following immunization (AEFI), clinicians should report them through the VAERS.[23]

Interprofessional coordination and collaboration among clinicians, specialists, pharmacists, nurses, and public health professionals can enhance patient outcomes when helping patients accept the MMR vaccine and prevent associated infections.