Drugs

, Volume 63, Issue 19, pp 2107–2126

Measles, Mumps, Rubella Vaccine (Priorix™ GSK-MMR)

A Review of its Use in the Prevention of Measles, Mumps and Rubella
Adis Drug Evaluation

Summary

Abstract

GSK-MMR (Priorix™ is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains.

GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9–27 months, and was as immunogenic as Merck-MMR (MMR® II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten™ recipients.

Coadministration of GSK-MMR with a varicella vaccine (Varilrix™ GSK-M-MR/V) did not significantly affect the immunogenicity of GSK-MMR.

A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1–2 years post-vaccination and were similar to those in Merck-MMR recipients.

The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4–6 or 11–12 years who had received a primary vaccination with Merck-MMR in their second year of life.

Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR).

GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability. In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.

Immunogenicity

The immunogenicity of GSK-MMR (Priorix™) has been evaluated as a primary vaccination in healthy infants aged 9–27 months and as a secondary vaccination in healthy children aged 4–6 or 11–12 years. All vaccinations consisted of a single subcutaneous injection into the upper arm; immunogenicity was evaluated 35–77 days post-vaccination.

GSK-MMR as a primary vaccination in infants was as immunogenic as Merck-MMR (MMR® H); 96.1–100%, 91.7–98.6% and 98.1–100% of GSK–MMR recipients seroconverted to antimeasles, antimumps and antirubella, compared with 91.5–100%, 93.6–97.9% and 97.9–100% of Merck-MMR recipients. Geometric mean antibody titres (GMTs) for measles, mumps and rubella antibodies were also similar in GSK-MMR or Merck-MMR recipients. Although antimeasles and antirubella seroconversion rates and GMTs were similar after vaccination with GSK-MMR or Berna-MMR (Triviraten™), antimumps seroconversion rates and GMTs were significantly higher in infants receiving GSK-MMR than in Berna-MMR recipients.

The immunogenicity of GSK-MMR as a primary vaccination was not significantly affected by coadministration with a varicella vaccine (Varilrix™; GSK-M-MR/V). An immune response to the measles, mumps and rubella components was seen in 96.1–100% of GSK-MMR recipients, compared with 91.9–100% in GSK-MMR/V recipients 60–70 days post-vaccination.

A persistent immune response to GSK-MMR was demonstrated in several 1- to 2-year follow-up studies. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1–2 years post-vaccination and were similar to those in Merck-MMR recipients.

GSK-MMR showed similar immunogenicity to Merck-MMR when used as a second dose in children aged 4–6 or 11–12 years who had received a primary MMR vaccination in their second year of life. There were no significant between-group differences in immune response rates or GMTs in children initially (at the time of the second dose) seronegative to measles, mumps or rubella antibodies in both studies. Among seropositive children aged 11–12 years, post-second-dose GMTs of antimumps and antirubella were significantly higher in GSK-MMR than Merck-MMR recipients but antimeasles GMTs were significantly higher in Merck-MMR recipients. In the younger children who were initially seropositive, post-vaccination immune response rates and GMTs were similar between groups.

The rubella Wistar RA 27/3 and measles Schwarz strains have well established protective efficacy, and it is expected that protection from mumps with the RIT 4385 mumps strain will be similar to that achieved with other mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR), from which the RIT 4385 strain was derived.

Tolerability

In most clinical studies comparing GSK-MMR vaccine with Merck-MMR vaccine as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events than Merck-MMR (e.g. injection-site pain, redness and swelling within 4 days). Indeed, the incidence of pain within the first 15 seconds or 30 minutes after vaccination in infants was significantly lower with GSK-MMR than Merck-MMR in the trials that reported such data. There were no significant between-group differences in the incidence of local adverse events within 3 days of the vaccination when GSK-MMR was compared with Berna-MMR or GSK-MMR/V. Severe pain was very rare, irrespective of which vaccine was administered.

The incidence of systemic adverse events (i.e. fever, rash and parotid gland swelling) after administration of GSK-MMR or Merck-MMR to infants was similar. Fever occurred most often during the second week post-vaccination. Berna-MMR, however, was associated with a significantly lower incidence of fever than GSK-MMR. The incidence of parotid gland swelling after administration of GSK-MMR, Merck-MMR or Berna-MMR was low (≤1.8%). In a pooled analysis, signs of suspected meningitis (e.g. febrile convulsions, vomiting, stiff neck, photophobia) were observed in three infants (0.1%) who received GSK-M-MR, and one recipient (0.1%) of Merck-MMR but were not considered related to the vaccines. Furthermore, there was no incidence of vaccine-related aseptic meningitis in a German 2-year post-marketing surveillance study during which time 1 575 936 doses of GSK-MMR were administered to children <15- years of age.

Coadministration of a varicella vaccine with GSK-MMR tended to increase the incidence of fever relative to GSK-MMR alone, and had no effect on or slightly increased the incidence of rash.

After administration of a second dose of GSK-MMR or Merck-MMR to children aged 4–6 or 11–12 years, significantly fewer GSK-MMR recipients experienced injection-site pain; the between-group incidences of redness and swelling were similar. The incidences of fever or rash were similar after administration of GSK-MMR or Merck-MMR as a second dose in children aged 4–6 or 11–12 years.

Dosage and Administration

GSK-MMR is indicated for active immunisation against measles, mumps and rubella for both the primary and secondary vaccination of children >12 months of age, although vaccination in younger infants (<12 months of age) may be indicated in some situations, such as in high risk areas. It can also be administered as a second dose in children, irrespective of which primary MMR vaccine was used.

The vaccine is available as a 0.5mL lyophilised mixed preparation of the attenuated Schwarz measles, RIT 4385 mumps and Wistar RA 27/3 rubella virus strains, and should be administered subcutaneously into the upper arm; it should never be administered intravascularly. GSK-MMR does not contain porcine gelatin, thus allowing those with religious objections to pig products to be administered GSK-MMR.

GSK-MMR is contraindicated in individuals with acute severe febrile illness, impaired immune responses, systemic hypersensitivity to neomycin or any other component of the vaccine, and in pregnant women.

Unless the reactions are anaphylactic in nature, individuals with egg allergies can be considered for vaccination with GSK-MMR. However, caution should be used when vaccinating individuals with a history, or family history, of allergic disease or convulsions. As with all injectable vaccines, appropriate medical treatment (e.g. adrenaline [epinephrine]) should be available for use in the rare event of anaphylaxis.

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© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, AucklandNew Zealand

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