Measles, Mumps, Rubella and Varicella vaccine (live) powder and solvent for suspension for injection 0.5ml pre-filled syringes

Background: Acute lymphoblastic leukemia is the most prevalent childhood cancer and the leading cause of cancer mortality before the age of 20. Although therapeutic advances have significantly improved survival, children and adolescents treated for acute lymphoblastic leukemia remain vulnerable to infections, largely preventable by vaccination, due to humoral and cellular immune dysfunction induced by disease and treatment. Materials and Methods: This systematic review, based on electronic databases, aims to evaluate antibody levels associated with potential protective immunity against vaccine antigens for diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, influenza, varicella-zoster virus, yellow fever, pneumococcal, and meningococcal diseases in children and adolescents treated for acute lymphoblastic leukemia after completion of chemotherapy. Results: A total of twenty-four studies published between 1981 and 2023 were included, comprising 1110 children and adolescents. Protective antibody levels ranged from 11% to 97% for diphtheria, 0% to 90% for pertussis, 20% to 100% for tetanus, and 11% to 95% for poliomyelitis. Haemophilus influenzae type b, protection ranged from 16.7% to 100%. Viral vaccines also showed heterogeneous responses, with protection rates of 25–79% for mumps, 16–86% for measles, 35–98% for rubella, and 23–75% for varicella-zoster virus. Antibody responses to pneumococcal and meningococcal vaccines were consistently low, with protection rates of 5–38% for pneumococcal studies and 12% in a single meningococcal study. Conclusions: This review found a consistent and clinically relevant loss of vaccine-induced immunity in children and adolescents treated for acute lymphoblastic leukemia. The recommendation of vaccine booster doses for this vulnerable population, irrespective of serological status, may represent a more practical approach to ensuring adequate post-chemotherapy treatment protection.

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A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P < 0.001) for MMRV versus MMR and 1.62 (95% CI 1.51, 1.70; P < 0.001) for MMRV versus MMR + V. Meanwhile, immune response to rubella component in MMRV group was slightly reduced, GMT ratios were 0.81 (95% CI 0.78, 0.85; P < 0.001) and 0.79 (95% CI 0.76, 0.83; P < 0.001), respectively. Well tolerated safety profiles were demonstrated except higher incidence of fever (relative risks 1.12-1.60) and measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence.

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Varicella is an acute, highly contagious infectious disease that primarily impacts young children with approximately 90% of cases occurring under the age of 15. Due to the high incidence of varicella infection, the potential for serious complications, and the significant economic and public health burden, vaccination of toddlers against varicella is included in routine vaccination programs in many countries. This study assessed the immunogenicity and safety of the investigational varicella vaccine (VNS) compared to a licensed, current standard-of-care vaccine. In this phase II, observer-blind, randomized, multicenter, controlled study, toddlers (12 to 15 months of age) received a single dose of the VNS vaccine (low, medium or high potency), or a single dose of the control vaccine. Hepatitis A and measles-mumps-rubella vaccines were co-administered to all participants. Pneumococcal conjugate vaccine was co-administered to all study participants as per national recommendations. Immunogenicity was assessed 43 days after vaccination; safety data were collected for up to 181 days post-vaccination. Overall, 800 participants were enrolled from 55 study centers across four countries (Estonia, Poland, Taiwan, and the United States), of whom 765 (95.6%) completed the study. Anti-varicella zoster virus glycoprotein E antibody geometric mean concentrations were generally comparable across study groups (960 mIU/ml [95% confidence interval [CI]: 843–1093], 1071 mIU/ml [952–1204] and 1555 mIU/ml [1407–1718] in the VNS-Low, VNS-Med and VNS-High groups, versus 1284 mIU/ml [1136–1453] in the control group). Seroresponse rates at Day 43 ranged from 93.6% in the VNS-Low group to 98.7% in the VNS-High group and 98.1% in the control group. The rate of occurrence, severity, and duration of adverse events and serious adverse events were similar across all study groups. These results show that the VNS vaccine was immunogenic with an acceptable safety profile following a single dose of all three potencies. Clinical trial registration number: NCT05084508 • Varicella is an acute, highly contagious infectious disease primarily affecting young children. • Three potencies of an investigational varicella vaccine were administered as a single dose. • The investigational varicella vaccine was compared to a standard of care vaccine. • All three potencies of the investigational vaccine formulation were immunogenic. • The safety profile of all three potencies of the investigational vaccine was acceptable.

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