Document text
Background on Measles, Mumps, Rubella, and Varicella
(MMRV) Vaccine
Arjun Srinivasan, MD, MS, MBA
Acting Chief Medical Officer
National Center for Immunization and Respiratory Di seases
ACIP Meeting
September 18, 2025 National Center for Immunization & Respiratory Dise ases
During the last major rubella epidemic in the U.S. (1964-1965), in 1 year:
–11,000 pregnant women lost their babies
–2,100 newborns died
–20,000 born with congenital rubella syndrome, causing deaf ness, heart defects
and developmental delay Measles, mumps, rubella, and varicella caused signi ficant
disease burden pre-vaccine in the United States
2
Before the introduction of measles vaccine (1963), each year an estimated:
–48,000 hospitalizations
–400-500 deaths
Each year in the early 1990s (before varicella vaccine):
–10,500-13,500 hospitalizations
–100-150 deaths
Mumps was the leading cause of viral encephalitis and sud den onset deafness
The introduction of monovalent measles, mumps, rube lla vaccines (1963-1969), followed by
trivalent MMR (1971), then monovalent varicella (19 95) and the quadrivalent MMRV (2005)
vaccines, coupled with attaining and maintaining hi gh coverage rates (>90%) in the United States
(U.S.) led to: Dramatic reductions in measles, mumps, rubella, and
varicella in the United States after introduction o f vaccines
Manual for the Surveillance of Vaccine-Preventable Diseases for Public Health | Manual for the Surveil lance of Vaccine-Preventable Diseases | CDC 3–Elimination of endemic measles in 2000
–Elimination of endemic rubella in 2004
–99% decline in mumps cases by early 2000
–97% decline in varicella incidence by 2019
Two options for measles, mumps, rubella, and varice lla vaccination: MMRV vaccine or
MMR vaccine + varicella vaccine
–Recommended as two doses: routine ages - 1st dose: 12-15 months; 2 nd dose: 4-6 years
The MMRV vaccine available in the U.S. (ProQuad, Me rck & Co, Inc) was licensed by FDA
in September 2005 based on noninferior immunogenicity of the antigenic components
compared with simultaneous administration of MMR va ccine and varicella vaccine
–Efficacy of the measles, mumps, rubella, and varicella compo nents of MMRV vaccine was
previously established in clinical studies with the monovalent vaccines
–Burden of disease for these diseases too low to perform efficacy clinical trials in the U.S. MMRV vaccine in the United States
4
Immunogenicity after the first dose of MMRV vaccine vs. MMR + varicella vaccines in
children aged 12 to 23 months was assessed in 4 randomized clinical trials
–5446 received MMRV, 2038 received MMR + varicella v accines at separate injection sites
–End points assessed (seroconversion rates and geome tric mean titers) were similar and met the pre-
established criteria for noninferiority 1
Immunogenicity after the second dose of MMRV vaccine vs. MMR vaccine (+/- varicella
vaccine) in children aged 4-6 years was assessed in 1 randomized clinical trial
–399 received MMRV, 205 received MMR + placebo, 195 received MMR + varicella vaccine; also met
pre-established criteria for noninferiority
2008-2009 ACIP Work Group assessment: given the non inferior immunogenicity,
effectiveness was assumed to be equal Clinical trials for MMRV vaccine
1Lower bound of the 95% CI for the difference in mea sles, mumps, and rubella seroconversion rates >-5.0% , lower bound of the 95% CI for the
difference in varicella seroprotection rates was eit her >-15% [one study] or >-10.0% [three studies] 5
Timeline of recommendations for MMRV vaccine use in
the United States
6September 2005
MMRV vaccine licensed for children
aged 12 months–12 years
Use of MMRV vaccine preferred over separate administration of MMR and
varicella vaccines February 2008
Vaccine safety finding from post-
licensure monitoring: increased risk
of febrile seizures after first dose of
MMRV vaccine June 2009
Updated recommendations
(next slide)
ACIP issued interim recommendation: removed
preference for MMRV use vs. MMR and varicella
vaccines for both dose 1 and dose 2 1
1At the time, MMRV vaccine had not been distributed in the U.S. since July 2007 because of manufacturin g constraints unrelated to safety or efficacy: Notice to
Readers: Update on Supply of Vaccines Containing Va ricella-Zoster Virus . MMRV vaccine became available again in the U.S. in 2012.
Use of Combination Measles, Mumps, Rubella, and Var icella Vaccine, MMWR 2010
Updated ACIP recommendations for MMRV vaccine use i n
the United States (current recommendations)
For the first dose of measles, mumps, rubella, and varicella
vaccination at age 12–47 months, either MMR vaccine and
varicella vaccine or MMRV vaccine may be used. Providers who
are considering administering the MMRV vaccine shou ld discuss
the benefits and risks of both vaccination options with the
parents or caregivers.
–CDC provided implementation guidance: unless the pa rent or caregiver
expresses a preference for the MMRV vaccine, CDC re commends that
MMR vaccine and varicella vaccine be administered f or the first dose in
this age group.
For the first dose at age ≥48 months and for the second dose at
any age (15 months–12 years), MMRV is generally preferred
over separate injections of MMR vaccine and varicel la vaccine
7
Use of Combination Measles, Mumps, Rubella, and Var icella Vaccine, MMWR 2010
No post-licensure vaccine effectiveness estimates a re available for the MMRV vaccine
used in the U.S.
–With measles and rubella being eliminated in the U. S., mumps and varicella at very low levels,
there were not enough cases of disease or outbreaks in children to assess vaccine
effectiveness in the U.S.
–Those vaccinated with MMRV or MMR and varicella vacc ines continue to have very low
rates of disease for measles, mumps, rubella, and v aricella in the U.S.
–There have been no reports to CDC indicating concern for lower MMRV vaccine ef fectiveness
compared to use of the separate component vaccines, consistent with the immunogenicity
results seen in the clinical trials Post-licensure effectiveness
8
MMRV vaccine accounts for 15% of first dose 1measles, mumps, rubella, and varicella
vaccination among children aged 19-35 months and 75% of second dose 2vaccination
among children aged 4-6 years
–First dose range by state: 5.1%-31.8%
–Second dose range by jurisdiction: 46%-96% MMRV vaccine utilization
1Data from National Immunization Survey-Child, 2023
2Data from 39 jurisdictions’ Immunization Informatio n Systems (IIS), children age 4-6 years by Dec 31, 2024 who received an MMR-
containing vaccine 9
MMRV vaccine is one of the two options for vaccination of U.S. children for protection
against measles, mumps, rubella, and varicella
The two vaccination options (MMRV vaccine or separa te injections of MMR vaccine and
varicella vaccine) are considered equivalent in terms of protection against disease
Due to the current recommendations, most MMRV vacci ne use in the U.S. is among children
age 4–6 years (for the second dose of MMR and varic ella vaccination)
Vaccination for measles, mumps, rubella, and varice lla has led to at least 97% reduction in
all four diseases compared with the pre-vaccine eraSummary
10
For more information, contact CDC 1-800-CDC-INFO (2 32-4636) TTY: 1-888-232-6348
www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not
necessarily represent the official position of the Centers for Disease Control and
Prevention.
•Bloch AB, Orenstein WA, Stetler HC, et al. Pediatri cs 1985;76:524-32. Health impact of measles
vaccination in the United States
•CDC. MMWR 2005;54:279–82. Elimination of rubella and congenital rubella syndr ome—United States,
1969–2004
•Marin, et al., JID, 2022, Monitoring Varicella Vaccine Impact on Varicella In cidence in the United States:
Surveillance Challenges and Changing Epidemiology, 1995–2019
•Marin, et al., JID, 2022, Decline in Severe Varicella Disease During the Unit ed States Varicella Vaccination
Program: Hospitalizations and Deaths, 1990–2019
•National Communicable Disease Center. Rubella surveillance. Bethesda, MD: US Department of Health,
Education, and Welfare; 1969.
•Shapiro, et al., JID, 2022, The Effectiveness of Varicella Vaccine: 25 Years of Postlicensure Experience in the
United States
•Witte JJ, Karchmer AW. Public Health Rep, 1968 Feb;8 3(2):5-100. Surveillance of mumps in the United
States as background for use of vaccine References: Pre-vaccine burden of measles, mumps, rubella, and varicella
•Measles : Measles Cases and Outbreaks: CDC Website: https://www.cdc.gov/measles/data-
research/index.html
•Mumps : Tappe J, et al. Vaccine 2024;42(25): Characteristics of reported mumps cases in the Unit ed Stats:
2018-2023.
•Rubella : Rubella in the United States: https://www.cdc.gov/rubella/vaccine-impact/index.ht ml
•Varicella : Shapiro E and Marin M. The effectiveness of varicella vaccine: 25 years of post-licensure experience
in the United States. The Journal of Infectious Diseases 2022: 226 (4): S425–S430 ; Marin M, Leung J, Anderson
TC, Lopez A. Monitoring Varicella Vaccine Impact on Varicella Incidence in the United States: Surveilla nce
Challenges and Changing Epidemiology, 1995–2019. The Journal of Infectious Diseases 2022: 226 (4): S392-
399 .References: Current/recent epidemiology for measles ,
mumps, rubella, and varicella