Status: approved; marketed

Organizations involved:

Merck & Co., Inc. – Manuf.; R&D; Tech.; USA mark.

Glaxo Wellcome plc – Europe mark.

Cross ref: See the Measles, Mumps and Rubella Virus Vaccine Live (M-M-R II) entry (#493).

Description: Mumps Virus Vaccine Live or Mumpsvax is a lyophilized (freeze-dried) formulation of live mumps virus, Jeryl Lynn (B level) strain, cultured in chicken embryo cell culture. Each 0.5 mL dose contains over 20,000 TCID50 of live mumps virus.

Mumpsvax is packaged in single-dose and 10-dose vials along with diluent for reconstitution and subcutaneous administration. Each dose also contains sorbitol (14.5 mg), sodium phosphate, sucrose (1.9 mg), sodium chloride, hydrolyzed gelatin (14.5 mg; presumed bovine source), human albumin (0.3 mg), fetal bovine serum (<1 ppm), traces of other buffer and media ingredients, and approximately 25 µg of neomycin. The product contains no preservatives. The live virus is temperature sensitive, and must be shipped at 10°C (50°F) or colder and be stored at 2-8°C (36-46°F) or colder.

Nomenclature: Mumps Virus Vaccine [BIO]; MUMPSVAX [TR]; Mumps Virus Vaccine Live [FDA USAN]; Mumps Virus Vaccine, Live [FDA former]; Mumps Virus Vaccine Live [USAN]; Mumps Virus Vaccine Live USP [USP]; mumps virus, Jeryl Lynn strain, live [SY]; NDC 0006-4753-00; NDC 0006-4584-00 [NDC]

History: Dow Chemical Co. held a license for manufacture of Mumps Vaccine Live from April 1974-June 1978. Companies previously licensed for manufacture of inactivated Mumps Vaccine were Eli Lilly & Co. (Jan. 1950-April 1977) and Lederle Labs. (June 1950-May 1978). Companies previously licensed for manufacture of Mumps Immune Globulin (Human) were Baxter Healthcare Corp. (Jan. 1958-June 1980) and Merck & Co., Inc. (Dec. 1982-March 1995).

Dr. M.R. Hilleman, Merck Sharp & Dohme, isolated and cultured the Jeryl Lynn strain of mumps virus from his daughter with the same name after she contracted the disease in 1963. The virus was attenuated by passage (repeated cycles of culturing) in chick-embryo cell cultures. Early clinical trials included testing in institutionalized retarded children (standard practice at the time; before current rigorous informed consent).

Companies.: Mumpsvax was developed and is manufactured by Merck & Co., Inc. (West Point, PA), FDA CBER/FDA est. lic. no. 0002. It is marketed in the U.S. by Merck & Co., Inc., and other countries by Merck & Co. affiliates. It is marketed in the U.K. by GlaxoSmithKline plc.

In 2006, a new vaccine manufacturing facility in Durham, NC, came came online, with completion/approval expected in 2010. M-M-R II, its component vaccines and Zostavax are manufactured there.

Manufacture: The manufacturing process for mumps vaccine is substantially similar to that of measles vaccine (see #491). This involves removal of embryos from the eggs of avian leukosis virus-free chickens; mincing, washing and trypsinization (use of trypsin enzyme to break up tissue) of the embryonic torsos to obtain suspended independent cells; placement of a specific number of cells in bottles; infection of the cells with mumps virus; and culture of the virus. The growth medium for the mumps virus is Medium 199 (a buffered salt solution containing vitamins and amino acids and supplemented with fetal bovine serum) containing SPGA (sucrose, phosphate, glutamate, and human albumin) as stabilizer and neomycin. After culture, fluids are harvested, clarified, stored, and lyophilized (freeze-dried). The cells, virus pools, fetal bovine serum, and Albumin (Human) are all screened for the absence of adventitious agents.

FDA class: Biologic PLA

CBER class: Viral And Rickettsial Vaccines

Approvals: Date = 19671228; first approval, PLA

Date = 19860106; license withdrawn under old proper name and granted (reissued) under new (current) FDA proper name

Indications: [portion of the "INDICATIONS AND USAGE” section from recent product insert/labeling]:

Recommended Vaccination Schedule

Mumpsvax is indicated for vaccination against mumps in persons 12 months of age or older. It is not recommended for infants younger than 12 months because they may retain maternal mumps neutralizing antibodies which may interfere with the immune response.

Individuals first vaccinated with Mumpsvax at 12 months of age or older should be revaccinated with M-M-R* II (Measles, Mumps, and Rubella Virus Vaccine Live) prior to elementary school entry. Revaccination may seroconvert primary failures or boost antibody titers of those individuals whose titers have declined. The Advisory Committee on Immunization Practices (ACIP) recommends administration of the first dose of M-M-R II at 12-15 months of age and administration of the second dose of M-M-R II at 4-6 years of age. In addition, some public health jurisdictions mandate the age for revaccination. Consult the complete text of applicable guidelines regarding routine revaccination including that of high-risk adult populations.

Status: Mumpsvax has been approved in various European countries, but not by the European Union.

Trials: Extensive clinical trials have shown the vaccine to be highly immunogenic and well tolerated. Efficacy of mumps vaccine was established in a series of double-blind controlled field trials, which demonstrated a high degree of protective efficacy. These studies also established that seroconversion (induction of neutralizing antibodies) in response to mumps vaccination paralleled protection from disease. A single injection results in mumps neutralizing antibodies in > 97% of children and > 93% of adults for at least 15 years. The close resemblance of vaccine-induced antibody responses to that of the natural infection suggests that vaccine protection may be life-long (although this hasn’t been completely established). Neutralizing and ELISA antibodies to mumps virus are still detectable in most individuals 11-13 years after primary vaccination.

Disease: Although rarely fatal, mumps virus infection causes flu-like illness and involvement of the parotid gland, with complications including encephalitis, meningitis, hearing loss, and other neurologic syndromes. The virus grows in the salivary (parotid) glands and the back of the throat and is usually benign. However, about half of children with wild-type mumps virus infection develop a mild case of meningitis (viral infection of the brain), with complications potentially including deafness and death. Mumps is associated as a cause of infertility in an estimated 13% of infected post-puberty males.

Before this vaccine, mumps was one of the most common diseases of childhood, with 200,000 cases annually among children annually in the U.S., with 90% of cases in children under age 14. In the U.S., from 2001-2005, an average of 265 mumps cases have been reported each year. Between 20 and 30 children died each year from complications of mumps. Since introduction of the vaccine in 1967, the number of reported mumps cases has dropped more than 99%, e.g., to only 751 in 1996. This drastic drop in cases occurred because the vaccine (usually as measles, mumps and rubella vaccine/M-M-R II) was adopted for universal use, i.e., it became a required pediatric vaccine

Permanently eliminating mumps, as has been done by vaccination for polio, is unlikely because 43% of nations worldwide do not vaccinate against the disease. And most countries that do vaccinate against mumps do not give two doses or have not been doing it for as long as the U.S. This is one reason why there was an outbreak of more than 70,000 cases in Britain from 2004 to 2006, even though the population is one-fifth the size of the U.S.

In spring 2006, outbreaks (or an epidemic) of mumps were occurring in the U.S. midwest, concentrated in Iowa. This illustrates that mumps is still a problem, with those not vaccinated or not fully vaccinated with the recommended two inoculations are susceptible to infection.      In Oct. 2006, the Centers for Disease Control and Prevention (CDC) reported that from Jan. 1, 2006 to Oct. 7, 2006, there were 5,783 confirmed or probable reports of mumps in the U.S. The highest rate of mumps occurred in people in the age range of 18-24 years. CDC suggested that M-M-R vaccines (M-M-R II) be offered along with influenza vaccines to those in this age group.

By spring 2008, it was widely reported that mumps was making a comeback in the U.S., despite widespread use of a second dose of mumps vaccine. In the April 11, 2008 New England Journal of Medicine, it was reported that there had been 6,584 cases nationwide and 85 hospitalizations,with no deaths, most concentrated in eight midwestern states and on college campuses. It was also reported that 84% of those between the ages of 18 and 24 who became ill in the outbreak had received the second recommended dose. A second dose of the vaccine is generally considered to be 88-95 percent effective. It was estimated that would have been tens of thousands of cases without vaccination. An improved vaccine will likely be needed. Multiple factors may have contributed to vaccine failure, including waning immunity, high population density and contact rates in colleges, and incomplete vaccine-induced immunity to wild virus

Merck & Co. has not made any changes to the mumps vaccine since it first became available in 1967. A third dose of the vaccine may be needed, especially among college students.

Medical: The dose for any age is 0.5 mL subcutaneously, preferably into the upper arm. The recommended age for primary vaccination is 12-15 months. This live vaccine produces a mild, non-communicable, mumps virus infection. Occasional adverse effects include mild fever (< 103˚F), cough, runny nose, diarrhea, and swollen lymph nodes. Fever over 103˚F is rare.

A study [Circulation 1997; 95(1):133-139] has indicated that mumps vaccine might not only eliminate the risk for mumps illness in recipients, but might also eliminate the risk for a heart condition, endocardial fibroelastosis, associated with mumps infection.

Market: Mumps vaccine is a universal pediatric vaccine, generally required by states and localities for entrance into school systems. The CDC reported in late 1999 that 99% of children entering kindergarden-1st grade (in 1995-1996 school year) had received mumps vaccination. In July 2004, CDC estimated that 93.0% (±0.6%) of infants/children had received one or more mumps vaccination in the form of M-M-R II.

M-M-R II and newer ProQuad combination vaccines are now primarily used, including in U.S. public vaccination programs, rather than monovalent Mumpsvax.

In Nov. 2004, the Centers for Disease Control and Prevention (CDC) reported that mumps vaccine coverage (the percentage of those vaccinated) among U.S. children entering school (kindergarten) in 2003-2004 was 96.0%. The National Immunization Program, CDC, had previously purchased Mumpsvax in bulk for $6.69/dose (contract ending 3/31/01).

The 2007 Average Wholesale Price (AWP) is $255.49/10 single-dose vials, with a Direct Price (Manufacturer’s discount price) of $214.16 ($215.94 in 2005; $208.90 in 2004). Prices include $.75/dose federal excise tax (funding federal vaccine liability insurance) charged by the manufacturer.