Safety and Immunogenicity of Human Serum Albumin-Free MMR Vaccine in US Children Aged 12-15 Months

Maurice A Mufson, Clemente Diaz, Michael Leonardi, Christopher J Harrison, Stanley Grogg, Antonio Carbayo, Simon Carlo-Torres, Robert JeanFreau, Ana Quintero-Del-Rio, Gisele Bautista, Michael Povey, Christopher Da Costa, Ouzama Nicholson, Bruce L Innis, Maurice A Mufson, Clemente Diaz, Michael Leonardi, Christopher J Harrison, Stanley Grogg, Antonio Carbayo, Simon Carlo-Torres, Robert JeanFreau, Ana Quintero-Del-Rio, Gisele Bautista, Michael Povey, Christopher Da Costa, Ouzama Nicholson, Bruce L Innis

Abstract

Background: M-M-R(TM)II (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (Priorix(TM), GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States.

Methods: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12-15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis A vaccine (HAV), varicella vaccine (VAR) and 7-valent pneumococcal conjugate vaccine (PCV7). Immune response to measles, mumps, and rubella viruses was evaluated at Day 42 post-vaccination. Incidence of solicited injection site, general, and serious adverse events was assessed.

Results: Seroresponse rates for MMR vaccine viral components in MMR-RIT lots were 98.3-99.2% (measles), 89.7-90.7% (mumps), and 97.5-98.8% (rubella), and for MMRII were 99.6%, 91.1%, and 100%, respectively. Immune responses to HAV, VAR, and PCV7 were similar when co-administered with any of the 3 MMR-RIT lots or MMRII. There were no apparent differences in solicited or serious adverse events among the 4 groups.

Conclusions: Immune responses were above threshold levels for projected protection against the 3 viruses from MMR-RIT lots with differing mumps virus titers. MMR-RIT had an acceptable safety profile when co-administered with HAV, VAR, and PCV7.

Clinical trials registration: NCT00861744; etrack; 111870.

Keywords: co-administration; immunogenicity; measles; mumps; rubella.

© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society.

Figures

Figure 1.
Figure 1.
Disposition of subjects in the total vaccinated cohort (TVC) (enrolled = 1259 subjects, randomized = 1224 subjects, vaccinated = 1220 subjects). Abbreviations: MMR, measles-mumps-rubella; SAE, serious adverse event; ATP, according-to-protocol.
Figure 2.
Figure 2.
Prevalence of any fever from Day 0 to Day 42 after vaccination (total vaccinated cohort). Abbreviation: MMR, measles-mumps-rubella.

References

    1. Centers for Disease Control and Prevention (CDC). Summary of Notifiable Diseases, United States, 1998. MMWR Morb Mortal Wkly Rep 1999; 47:ii–92.
    1. Centers for Disease Control and Prevention (CDC). Notes from the field: Measles outbreak—Hennepin County, Minnesota, February-March 2011. MMWR Morb Mortal Wkly Rep 2011; 60:421.
    1. Centers for Disease Control and Prevention (CDC). Measles: United States, January-May 20, 2011. MMWR Morb Mortal Wkly Rep 2011; 60:666–8.
    1. Dayan GH, Quinlisk MP, Parker AA, et al. Recent resurgence of mumps in the United States. N Engl J Med 2008; 358:1580–9.
    1. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics 2007; 120:221–31.
    1. American Academy of Pediatrics Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics 2000; 106:362–6.
    1. Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006; 55:1–23.
    1. Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1998; 47:1–57.
    1. Committee on Infectious Diseases; American Academy of Pediatrics. Policy statement—recommended childhood and adolescent immunization schedules—United States, 2011. Pediatrics 2011; 127:387–8.
    1. . Immunisation against infectious disease: Mumps: the green book, chapter 23. Available at: Accessed February 12, 2014.
    1. Offit PA, Jew RK. Addressing parents’ concerns: do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 2003; 112:1394–7.
    1. EMEA–CHMP. EMEA–CHMP Position Statement on Creutzfeldt–Jakob Disease and Plasma-derived and Urine-derived Medicinal Products. 2004. Available at: Accessed February 12, 2014.
    1. EMEA–CHMP. EMEA–CHMP Guideline on the Investigation of Manufacturing Processes for Plasma-derived Medicinal Products With Regard to VCJD Risk. 2004. Available at: Accessed February 12, 2014.
    1. Merck & Co. I. M-M-R(R) II (Measles, Mumps, and Rubella Virus Vaccine Live). December 2010. Available at: Accessed February 12, 2014.
    1. GlaxoSmithKline. HAVRIX (Hepatitis A Vaccine). Highlights of Prescribing Information. HVX:35PI. July 2011. Available at: Accessed February 12, 2014.
    1. Merck & Co. I. VARIVAX(R). Varicella Virus Vaccine Live. Highlights of Prescribing Information. August 2011. Available at: Accessed February 12, 2014.
    1. Wyeth Pharmaceuticals Inc. Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM197 Protein). July 2009. Available at: Accessed February 12, 2014.
    1. Sato H, Albrecht P, Hicks JT, Meyer BC, Ennis FA. Sensitive neutralization test for virus antibody. 1. Mumps antibody. Arch Virol 1978; 58:301–11.
    1. Dodet M, Dessy F, Parent I, Gerard P. Use of a neutralization assay as an alternative for assessing mumps immunization status. In: Program and Abstracts of the 24th Annual Meeting of the European Society for Pediatric Infectious Diseases (Basel, Switzerland) 2006. Abstract 387.
    1. Poolman JT, Frasch CE, Kayhty H, Lestrate P, Madhi SA, Henckaerts I. Evaluation of pneumococcal polysaccharide immunoassays using a 22F adsorption step with serum samples from infants vaccinated with conjugate vaccines. Clin Vaccine Immunol 2010; 17:134–42.
    1. Kiepiela P, Coovadia HM, Loening WE, Coward P, Abdool Karim SS. Loss of maternal measles antibody in black South African infants in the first year of life—implications for age of vaccination. S Afr Med J 1991; 79:145–8.
    1. Skendzel LP. Rubella immunity. Defining the level of protective antibody. Am J Clin Pathol 1996; 106:170–4.
    1. Klein NP, Fireman B, Yih WK, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatr 2010; 126:e1–8.
    1. Bernstein H, Marchant C, Rathfon H, Marchand P, Kimura A. Safety and immunogenicity of a new, live, attenuated combined measles, mumps and rubella vaccine in healthy U.S. children 12 to 18 months of age. Antimicrob Agents Chemother 1999; 39:719 (abstract no. 1086).
    1. Usonis V, Bakasenas V, Chitour K, Clemens R. Comparative study of reactogenicity and immunogenicity of new and established measles, mumps and rubella vaccines in healthy children. Infection 1998; 26:222–6.
    1. Usonis V, Bakasenas V, Kaufhold A, Chitour K, Clemens R. Reactogenicity and immunogenicity of a new live attenuated combined measles, mumps and rubella vaccine in healthy children. Pediatr Infect Dis J 1999; 18:42–8.
    1. Gatchalian S, Cordero-Yap L, Lu-Fong M, et al. A randomized comparative trial in order to assess the reactogenicity and immunogenicity of a new measles mumps rubella (MMR) vaccine when given as a first dose at 12-24 months of age. Southeast Asian J Trop Med Public Health 1999; 30:511–7.
    1. Lee CY, Tang RB, Huang FY, Tang H, Huang LM, Bock HL. A new measles mumps rubella (MMR) vaccine: a randomized comparative trial for assessing the reactogenicity and immunogenicity of three consecutive production lots and comparison with a widely used MMR vaccine in measles primed children. Int J Infect Dis 2002; 6:202–9.
    1. Hishiyama M, Tsurudome M, Ito Y, Yamada A, Sugiura A. Complement-mediated neutralization test for determination of mumps vaccine-induced antibody. Vaccine 1988; 6:423–7.
    1. Lim FS, Han HH, Bock HL. Safety, reactogenicity and immunogenicity of the live attenuated combined measles, mumps and rubella vaccine containing the RIT 4385 mumps strain in healthy Singaporean children. Ann Acad Med Singapore 2007; 36:969–73.

Source: PubMed

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