Measles, Mumps, Rubella Vaccine (PRIORIX): Recommendations of the Advisory Committee on Immunization Practices  United States, 2022

 [bib_ref] Recommendation of the Advisory Committee on Immunization Practices for use of a..., Marin [/bib_ref] [bib_ref] Maintenance of measles elimination status in the United States for 20 years..., Mathis [/bib_ref] [bib_ref] Recommendation of the Advisory Committee on Immunization Practices for use of a..., Marin [/bib_ref] 

## Summary of key findings
SAEs related to administration of PRIORIX were assessed using findings from four randomized controlled clinical trials at the licensed U.S. potency of PRIORIX and one Cochrane review with PRIORIX at any potency [bib_ref] Immunogenicity and reactogenicity of a new measles, mumps and rubella vaccine when..., Gothefors [/bib_ref] [bib_ref] Safety and immunogenicity of human serum albumin-free MMR vaccine in US children..., Mufson [/bib_ref] [bib_ref] Vaccines for measles, mumps, rubella, and varicella in children, Pietrantonj [/bib_ref]. Four additional observational studies and one additional systematic review addressed additional adverse events of interest (i.e., rate of febrile seizures, aseptic meningitis, and ITP) [bib_ref] A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and..., Farrington [/bib_ref] [bib_ref] Vaccine Safety Datalink Team. Risk of immune thrombocytopenic purpura after measles-mumpsrubella immunization..., France [/bib_ref] [bib_ref] Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United..., Miller [/bib_ref] [bib_ref] The risk of immune thrombocytopenic purpura after vaccination in children and adolescents, O&apos;leary [/bib_ref] [bib_ref] Enhancing global vaccine pharmacovigilance: proof-of-concept study on aseptic meningitis and immune thrombocytopenic..., Perez-Vilar [/bib_ref]. Outcomes for PRIORIX were compared with those for M-M-R II. In the four randomized controlled clinical trials at the U.S. potency of PRIORIX, safety profiles among 1,960 subjects receiving 1 or 2 doses of PRIORIX were compared with those among 933 subjects randomized to receive 1 or 2 doses of M-M-R II. The subjects ranged in age from 12 months to 12 years, with 90% aged 12-15 months. The frequency of vaccine-related SAEs was similar across the vaccine These studies included coadministration of recommended age-appropriate vaccines, and all found the differences in rates of febrile seizures between the two vaccines to be nonsignificant [bib_ref] Safety and immunogenicity of human serum albumin-free MMR vaccine in US children..., Mufson [/bib_ref] [bib_ref] Immunogenicity and safety of a measles-mumps-rubella vaccine administered as a first dose..., Klein [/bib_ref]. Similarly, the time course of fever was comparable for both vaccines across all studies, with most instances observed 5-12 days postvaccination (Remon Abu-Elyazeed, MD, PhD, GlaxoSmithKline Biologicals, personal communication, . No evidence of an association of aseptic meningitis with MMR vaccination was reported in the literature for vaccines containing Jeryl Lynn or Jeryl Lynnderived mumps strains, which are included in both M-M-R II and PRIORIX for immunization against mumps [bib_ref] Vaccines for measles, mumps, rubella, and varicella in children, Pietrantonj [/bib_ref] [bib_ref] Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United..., Miller [/bib_ref].
ITP is associated with the receipt of live attenuated measles vaccines [bib_ref] Vaccines for measles, mumps, rubella, and varicella in children, Pietrantonj [/bib_ref] [bib_ref] Vaccine Safety Datalink Team. Risk of immune thrombocytopenic purpura after measles-mumpsrubella immunization..., France [/bib_ref] [bib_ref] The risk of immune thrombocytopenic purpura after vaccination in children and adolescents, O&apos;leary [/bib_ref] [bib_ref] Enhancing global vaccine pharmacovigilance: proof-of-concept study on aseptic meningitis and immune thrombocytopenic..., Perez-Vilar [/bib_ref]. In the four randomized controlled clinical trials at the U.S. potency of PRIORIX, one case of ITP was identified among 1,960 PRIORIX recipients and one case among 933 M-M-R II recipients. From a previous postmarketing study conducted in the United States, the rate of ITP after M-M-R II is estimated at 2.5 per 100,000 doses [bib_ref] Vaccine Safety Datalink Team. Risk of immune thrombocytopenic purpura after measles-mumpsrubella immunization..., France [/bib_ref]. However, strain-or vaccine formulation-specific data on ITP risk are sparse. Based on the clinical trials and the literature [bib_ref] Vaccines for measles, mumps, rubella, and varicella in children, Pietrantonj [/bib_ref] [bib_ref] Vaccine Safety Datalink Team. Risk of immune thrombocytopenic purpura after measles-mumpsrubella immunization..., France [/bib_ref] [bib_ref] The risk of immune thrombocytopenic purpura after vaccination in children and adolescents, O&apos;leary [/bib_ref] [bib_ref] Enhancing global vaccine pharmacovigilance: proof-of-concept study on aseptic meningitis and immune thrombocytopenic..., Perez-Vilar [/bib_ref] , the rates of ITP after vaccination were considered similar for PRIORIX and M-M-R II.
Short-term humoral immunity was assessed using data from 13 randomized controlled trials [bib_ref] Immunogenicity and reactogenicity of a new measles, mumps and rubella vaccine when..., Gothefors [/bib_ref] [bib_ref] Safety and immunogenicity of human serum albumin-free MMR vaccine in US children..., Mufson [/bib_ref] [bib_ref] Immunogenicity and safety of a measles-mumps-rubella vaccine administered as a first dose..., Klein [/bib_ref] [bib_ref] Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered..., Abu-Elyazeed [/bib_ref] [bib_ref] A randomized comparative trial in order to assess the reactogenicity and immunogenicity..., Gatchalian [/bib_ref] [bib_ref] A new measles mumps rubella (MMR) vaccine: a randomized comparative trial for..., Lee [/bib_ref] [bib_ref] Reappraisal of MMR vaccines currently used in Korea, Lee [/bib_ref] [bib_ref] Comparative study of reactogenicity and immunogenicity of new and established measles, mumps..., Usonis [/bib_ref] [bib_ref] Neutralization activity and persistence of antibodies induced in response to vaccination with..., Usonis [/bib_ref] [bib_ref] Reactogenicity and immunogenicity of a new live attenuated combined measles, mumps and..., Usonis [/bib_ref] , four at the licensed U.S. potency of PRIORIX, and nine at a lower potency of PRIORIX used in other countries. Serologic response thresholds were achieved for all three antigens in all studies. Antibodies in all studies were more than 8.8-fold higher than the predefined seroresponse threshold for measles (200 mIU per mL; correlate of protection 120 mIU per mL) and more than 4.2-fold higher than the rubella correlate (10 IU per mL). Although an antibody correlate of protection has not been established for mumps, the anti-mumps antibody level was 3.3-fold higher than the mumps seroconversion threshold (10 IU per mL). The four studies conducted with PRIORIX at the U.S. potency found no significant difference in anti-measles, anti-mumps, or anti-rubella geometric mean concentrations (GMC) after the first dose between PRIORIX and M-M-R II recipients. Among the nine studies at a lower PRIORIX potency, eight showed no statistically significant difference between anti-measles or anti-rubella GMC levels, and seven showed no statistically significant difference between anti-mumps GMC levels. One study reported on persistence of the humoral immune response (2 years after vaccination) and found no difference between vaccines [bib_ref] Two-year antibody persistence in children vaccinated at 12-15 months with a measlesmumps-rubella..., Berry [/bib_ref]. None of the four studies that reported on GMC after a second dose noted a significant difference for any antigen at any potency after a second dose between PRIORIX or M-M-R II recipients [bib_ref] Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered..., Abu-Elyazeed [/bib_ref].
Additional data reviewed within the EtR framework included findings from a focus group conducted with state immunization managers and a survey of pediatric and general practitioners regarding the feasibility for use and acceptability of PRIORIX. Both the focus group and the survey findings supported the interchangeability of M-M-R II and PRIORIX and the benefit of having a second MMR vaccine option available.

## Summary
What is already known about this topic?
Since 1978, M-M-R II has been the only measles, mumps, and rubella (MMR) combination vaccine used in the United States. In June 2022, the Food and Drug Administration licensed an additional MMR vaccine, PRIORIX.
What is added by this report?
The Advisory Committee on Immunization Practices recommends PRIORIX as an additional option to prevent MMR according to existing vaccine recommendations and off-label uses.
What are the implications for public health practice?
Both vaccines are interchangeable for all indications for which MMR vaccination is recommended. Availability from multiple manufacturers safeguards U.S. vaccine supply.

## Rationale for recommendation
Given the similarities in potency and vaccine components, and evidence for similar safety and immunogenicity, as well as stakeholder support, PRIORIX and M-M-R II are considered fully interchangeable, including for all off-label recommended uses. Either vaccine may be administered in any situation in which an MMR virus-containing vaccine is indicated. Two interchangeable vaccines from different manufacturers will help safeguard vaccine supply in the United States to maintain measles and rubella elimination and mitigate mumps cases and outbreaks.

## Acip recommendation
PRIORIX is recommended according to the existing MMR recommended schedules and off-label uses [bib_ref] Recommendation of the Advisory Committee on Immunization Practices for use of a..., Marin [/bib_ref] as an option to prevent measles, mumps, and rubella.

## Clinical guidance
PRIORIX is supplied as a single-dose vial of lyophilized antigen to be reconstituted with the accompanying prefilled syringe of sterile water diluent. A single dose after reconstitution is approximately 0.5 mL. PRIORIX is formulated without preservatives and is administered as subcutaneous injection (the same as M-M-R II).
PRIORIX may be used according to the existing MMR recommendations for both on-and off-label use for prevention of measles, mumps, and rubella   [bib_ref] Recommendation of the Advisory Committee on Immunization Practices for use of a..., Marin [/bib_ref]. For routine vaccination, 2 doses are recommended, the first at age 12-15 months, and the second at age 4-6 years. For catch-up vaccination of previously unvaccinated children and adolescents, 2 doses   No direct evidence for PRIORIX for off-label uses; recommendation is based on existing ACIP recommendations and comparative use of M-M-R II in similar situations.
should be administered 4 weeks apart. Before international travel, infants aged 6-11 months should receive a single dose. Travelers aged 12 months who have not received 2 doses of MMR should receive 2 doses separated by 28 days. During a measles outbreak, infants aged 6-11 months should receive a single dose of MMR. For measles postexposure prophylaxis in unvaccinated persons, 1 dose of MMR should be administered within 72 hours of exposure to a person with infectious measles, and the 2-dose series (i.e., the second of 2 MMR doses) should be completed 28 days later. During mumps outbreaks, a third dose of MMR is recommended for persons identified by public health authorities as being part of a group or population at increased risk for acquiring mumps because of an outbreak.

## Interchangeability
PRIORIX and M-M-R II are fully interchangeable. ACIP General Best Practices states a preference that doses of vaccine in a series come from the same manufacturer; however, vaccination should not be deferred when the manufacturer of the previously administered vaccine is unknown or when the vaccine from the same manufacturer is unavailable. Studies have shown that PRIORIX is safe and immunogenic when administered as a second dose after M-M-R II [bib_ref] Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered..., Abu-Elyazeed [/bib_ref].

## Timing of vaccination and coadministration with other vaccines
PRIORIX can be administered concomitantly, at different anatomic sites, with other routine childhood vaccines. Concomitant administration of PRIORIX with other live and nonlive vaccines   has been studied; results indicated no safety concerns or evidence for interference in the immune response to either [bib_ref] Safety and immunogenicity of human serum albumin-free MMR vaccine in US children..., Mufson [/bib_ref] [bib_ref] Immunogenicity and safety of a measles-mumps-rubella vaccine administered as a first dose..., Klein [/bib_ref] [bib_ref] Immunogenicity and safety of a second dose of a measles-mumps-rubella vaccine administered..., Abu-Elyazeed [/bib_ref]. Additional live virus vaccines not administered on the same day should be separated by 4 weeks.

## Precautions and contraindications
Before administering PRIORIX, health care providers should consult the package insert for precautions, warnings, and contraindications. Contraindications for PRIORIX are the same as those for M-M-R II. PRIORIX should not be administered to persons with a history of severe allergic reactions (e.g., anaphylaxis) to any component of the vaccine or after a previous dose of any measles, mumps, and rubella virus-containing vaccine (unlike M-M-R II, PRIORIX does   Among children aged 12-15 months: with 13-valent pneumococcal conjugate vaccine (PCV13-Prevnar), Varivax (VAR), Havrix (HAV), and 7-valent pneumococcal conjugate vaccine (PCV7). Among children aged 4-6 years: with Kinrix (DTaP-IPV) and Varivax. not contain gelatin); persons with severe humoral or cellular (primary or acquired) immunodeficiency; or women who are pregnant. Pregnancy should be avoided for 1 month after receipt of MMR. Additional information on warnings and precautions can be found in the package insert and previous vaccine recommendations.

## Reporting of vaccine adverse events
Adverse events following administration of any vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS). Reports can be submitted to VAERS online, by fax, or by mail. Additional information about VAERS is available by telephone (1-800-822-7967) or online (https:// vaers.hhs.gov). Any future revisions to this ACIP recommendation will be dictated by reported adverse events and new research evidence.
[table] TABLE: Components and infectious dosage* of measles, mumps, and rubella vaccines  licensed in the United States [/table]