MMR Vaccine (PRIORIX): Recommendations of the ACIP

Abstract and Introduction

Introduction

Vaccination is the main means for preventing measles, mumps, and rubella virus infections and their related complications.^[1,2] Achieving and maintaining high 2-dose measles, mumps, and rubella vaccination coverage in the United States has led to elimination of endemic measles in 2000, rubella and congenital rubella syndrome in 2004, and a sharp decrease in mumps cases. However, measles and rubella remain endemic in many countries, leading to importations of cases and occasional local transmission within the United States.^[3] Reported U.S. mumps cases declined >99% from the prevaccine period;^[4] however, mumps is endemic worldwide, and since 2006, the number of mumps cases and mumps outbreaks has increased in the United States, with wider geographic spread since 2016.^[4] Given the risk for importation of measles and rubella and the resurgence of mumps, maintaining high measles, mumps, and rubella (MMR) vaccination coverage is important. Since 1978, only one MMR vaccine, M-M-R II (Merck and Co., Inc.), has been available in the United States. On June 6, 2022, the Food and Drug Administration approved a second MMR vaccine, PRIORIX (GlaxoSmithKline Biologicals), for the prevention of measles, mumps, and rubella in persons aged ≥12 months. The three live attenuated viruses contained in PRIORIX are genetically similar or identical to the corresponding components in M-M-R II (Table).^[5–7] On June 23, 2022, the Advisory Committee on Immunization Practices (ACIP) unanimously recommended PRIORIX as an option to prevent measles, mumps, and rubella according to the existing recommended schedules and for off-label uses (i.e., indications not included in the package insert)*.^[1,2] ACIP considered PRIORIX to be safe, immunogenic, and noninferior to M-M-R II. Both PRIORIX and M-M-R II are fully interchangeable for all indications for which MMR vaccination is recommended. This report contains ACIP recommendations specific to PRIORIX and supplements the existing ACIP recommendations for MMR use.^[1,2]

During January–June 2022, the ACIP Measles, Mumps, and Rubella Vaccine Work Group (Work Group) held monthly conference calls to review and assess the safety and immunogenicity of PRIORIX and to discuss implementation issues. The Work Group identified the following outcomes of interest for evaluation: 1) prevention of measles, mumps, and rubella; 2) short-term humoral immunity; 3) persistence of the humoral immune response; 4) reactogenicity of grade 3 or higher^†; 5) vaccine-related serious adverse events (SAEs)^§; and 6) additional adverse events of interest (i.e., rate of febrile seizures, aseptic meningitis, and immune thrombocytopenic purpura [ITP]). SAEs and reactogenicity of grade 3 or higher were evaluated only in studies conducted at or above the licensed U.S. potency for PRIORIX. Additional adverse events and immunogenicity were evaluated at any potency of PRIORIX.^¶ The Evidence to Recommendations (EtR) framework was used to organize Work Group deliberations.**

Data on the outcomes of interest were summarized based on findings from a systematic review of the literature in PubMed, Medline, Embase, Scopus, Cochrane databases, and clinicaltrials.gov. Search terms for the literature review, study inclusion criteria, and supporting evidence are available online. All studies conducted with PRIORIX at the U.S. potency were included. For studies conducted at a potency different from that for the U.S.-licensed product, the evidence reviewed was restricted to the highest level of evidence: experimental design (i.e., randomized controlled clinical trials) or high-quality reviews (i.e., Cochrane reviews, systematic reviews, or meta-analyses).

The Work Group reviewed all included studies of PRIORIX to assess the safety and immunogenicity of PRIORIX and discussed implementation issues. Summaries of Work Group discussions were presented to ACIP on February 23, 2022 and on June 23, 2022. At the June 2022 meeting, a proposed recommendation was presented to the committee and, after a public comment period, was unanimously approved by the voting ACIP members. PRIORIX is recommended according to the existing recommended schedules and off-label uses as an option to prevent measles, mumps, and rubella.

Table. Components and infectious dosage* of measles, mumps, and rubella vaccines ^† licensed in the United States
Vaccine characteristic	Viral component
Vaccine characteristic	Measles	Mumps	Rubella
M-M-R II
Strain	Enders' Edmonston	Jeryl Lynn (B level)	Wistar RA 27/3
Infectious dose, minimum and maximum release potencies	≥10^3.0–10^3.8 TCID₅₀	≥10^4.1–10^4.8 TCID₅₀	≥10^3.0–10^3.6 TCID₅₀
PRIORIX
Strain	Schwarz	RIT4385	Wistar RA 27/3
Infectious dose, minimum and maximum release potencies	≥10^3.4–10^4.5 CCID₅₀	≥10^4.2–10^5.6 CCID₅₀	≥10^3.3–10^4.4 CCID₅₀

Abbreviations: CCID₅₀ = cell culture infectious dose; TCID₅₀ = tissue culture infectious dose.
*TCID₅₀ and CCID₅₀ are closely related measures describing how much infectious virus is contained in a vaccine product.
^†Both the measles and rubella strains in M-M-R II and PRIORIX are 100% identical on a nucleotide level. The Jeryl Lynn strain used in M-M-R II is a mixture of two viral lineages, JL1 and JL2. RIT4385 is a pure clone of JL1 and is 100% identical on a protein level to M-M-R II's JL1 component.