Vaccine Information: VARIVAX (Page 3 of 4)

14.2 Immunogenicity

In clinical trials, varicella antibodies have been evaluated following vaccination with formulations of VARIVAX containing attenuated virus ranging from 1000 to 50,000 PFU per dose in healthy individuals ranging from 12 months to 55 years of age {2,9}.

One-Dose Regimen in Children

In prelicensure efficacy studies, seroconversion was observed in 97% of vaccinees at approximately 4 to 6 weeks postvaccination in 6889 susceptible children 12 months to 12 years of age. Titers ≥5 gpELISA units/mL were induced in approximately 76% of children vaccinated with a single dose of vaccine at 1000 to 17,000 PFU per dose. Rates of breakthrough disease were significantly lower among children with VZV antibody titers ≥5 gpELISA units/mL compared with children with titers <5 gpELISA units/mL.

Two-Dose Regimen in Children

In a multicenter study, 2216 healthy children 12 months to 12 years of age received either 1 dose of VARIVAX or 2 doses administered 3 months apart. The immunogenicity results are shown in Table 3.

Table 3: Summary of VZV Antibody Responses at 6 Weeks Postdose 1 and 6 Weeks Postdose 2 in Initially Seronegative Children 12 Months to 12 Years of Age (Vaccinations 3 Months Apart)
VARIVAX1-Dose Regimen(N=1114) VARIVAX2-Dose Regimen (3 months apart)(N=1102)
6 Weeks Postvaccination (n=892) 6 Weeks Postdose 1 (n=851) 6 Weeks Postdose 2 (n=769)
N = Number of subjects vaccinated.
n = Number of subjects included in immunogenicity analysis.
Seroconversion Rate 98.9% 99.5% 99.9%
Percent with VZV Antibody Titer ≥5 gpELISA units/mL 84.9% 87.3% 99.5%
Geometric mean titers in gpELISA units/mL (95% CI) 12.0(11.2, 12.8) 12.8(11.9, 13.7) 141.5(132.3, 151.3)

The results from this study and other studies in which a second dose of VARIVAX was administered 3 to 6 years after the initial dose demonstrate significant boosting of the VZV antibodies with a second dose. VZV antibody levels after 2 doses given 3 to 6 years apart are comparable to those obtained when the 2 doses are given 3 months apart.

Two-Dose Regimen in Adolescents and Adults

In a multicenter study involving susceptible adolescents and adults 13 years of age and older, 2 doses of VARIVAX administered 4 to 8 weeks apart induced a seroconversion rate of approximately 75% in 539 individuals 4 weeks after the first dose and of 99% in 479 individuals 4 weeks after the second dose. The average antibody response in vaccinees who received the second dose 8 weeks after the first dose was higher than that in vaccinees who received the second dose 4 weeks after the first dose. In another multicenter study involving adolescents and adults, 2 doses of VARIVAX administered 8 weeks apart induced a seroconversion rate of 94% in 142 individuals 6 weeks after the first dose and 99% in 122 individuals 6 weeks after the second dose.

14.3 Persistence of Immune Response

One-Dose Regimen in Children

In clinical studies involving healthy children who received 1 dose of vaccine, detectable VZV antibodies were present in 99.0% (3886/3926) at 1 year, 99.3% (1555/1566) at 2 years, 98.6% (1106/1122) at 3 years, 99.4% (1168/1175) at 4 years, 99.2% (737/743) at 5 years, 100% (142/142) at 6 years, 97.4% (38/39) at 7 years, 100% (34/34) at 8 years, and 100% (16/16) at 10 years postvaccination.

Two-Dose Regimen in Children

In recipients of 1 dose of VARIVAX over 9 years of follow-up, the geometric mean titers (GMTs) and the percent of subjects with VZV antibody titers ≥5 gpELISA units/mL generally increased. The GMTs and percent of subjects with VZV antibody titers ≥5 gpELISA units/mL in the 2-dose recipients were higher than those in the 1-dose recipients for the first year of follow-up and generally comparable thereafter. The cumulative rate of VZV antibody persistence with both regimens remained very high at year 9 (99.0% for the 1-dose group and 98.8% for the 2-dose group).

Two-Dose Regimen in Adolescents and Adults

In clinical studies involving healthy adolescents and adults who received 2 doses of vaccine, detectable VZV antibodies were present in 97.9% (568/580) at 1 year, 97.1% (34/35) at 2 years, 100% (144/144) at 3 years, 97.0% (98/101) at 4 years, 97.4% (76/78) at 5 years, and 100% (34/34) at 6 years postvaccination.

A boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella, which could account for the apparent long-term persistence of antibody levels in these studies.

14.4 Studies with Other Vaccines

Concomitant Administration with M-M-R II

In combined clinical studies involving 1080 children 12 to 36 months of age, 653 received VARIVAX and M-M-R II concomitantly at separate injection sites and 427 received the vaccines six weeks apart. Seroconversion rates and antibody levels to measles, mumps, rubella, and varicella were comparable between the two groups at approximately six weeks postvaccination.

Concomitant Administration with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) and Oral Poliovirus Vaccine (OPV)

In a clinical study involving 318 children 12 months to 42 months of age, 160 received an investigational varicella-containing vaccine (a formulation combining measles, mumps, rubella, and varicella in one syringe) concomitantly with booster doses of DTaP and OPV (no longer licensed in the United States). The comparator group of 144 children received M-M-R II concomitantly with booster doses of DTaP and OPV followed by VARIVAX six weeks later. At six weeks postvaccination, seroconversion rates for measles, mumps, rubella, and VZV and the percentage of vaccinees whose titers were boosted for diphtheria, tetanus, pertussis, and polio were comparable between the two groups. Anti-VZV levels were decreased when the investigational vaccine containing varicella was administered concomitantly with DTaP {19}. No clinically significant differences were noted in adverse reactions between the two groups.

Concomitant Administration with PedvaxHIB®

In a clinical study involving 307 children 12 to 18 months of age, 150 received an investigational varicella-containing vaccine (a formulation combining measles, mumps, rubella, and varicella in one syringe) concomitantly with a booster dose of PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)], while 130 received M-M-R II concomitantly with a booster dose of PedvaxHIB followed by VARIVAX 6 weeks later. At six weeks postvaccination, seroconversion rates for measles, mumps, rubella, and VZV, and GMTs for PedvaxHIB were comparable between the two groups. Anti-VZV levels were decreased when the investigational vaccine containing varicella was administered concomitantly with PedvaxHIB {20}. No clinically significant differences in adverse reactions were seen between the two groups.

Concomitant Administration with M-M-R II and COMVAX

In a clinical study involving 822 children 12 to 15 months of age, 410 received COMVAX, M-M-R II, and VARIVAX concomitantly at separate injection sites, and 412 received COMVAX followed by M-M-R II and VARIVAX given concomitantly at separate injection sites, 6 weeks later. At 6 weeks postvaccination, the immune responses for the subjects who received the concomitant doses of COMVAX, M-M-R II, and VARIVAX were similar to those of the subjects who received COMVAX followed 6 weeks later by M-M-R II and VARIVAX with respect to all antigens administered. There were no clinically important differences in reaction rates when the three vaccines were administered concomitantly versus six weeks apart.

15 REFERENCES

  1. CDC: General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 55(No. RR-15): 1-47, 2006.
  2. Weibel, R.E.; et al.: Live Attenuated Varicella Virus Vaccine. Efficacy Trial in Healthy Children. N Engl J Med. 310(22): 1409-1415, 1984.
  3. Arbeter, A.M.; et al.: Varicella Vaccine Trials in Healthy Children. A Summary of Comparative and Follow-up Studies. Am J Dis Child. 138: 434-438, 1984.
  4. Weibel, R.E.; et al.: Live Oka/Merck Varicella Vaccine in Healthy Children. Further Clinical and Laboratory Assessment. JAMA. 254(17): 2435-2439, 1985.
  5. Chartrand, D.M.; et al.: New Varicella Vaccine Production Lots in Healthy Children and Adolescents. Abstracts of the 1988 Inter-Science Conference Antimicrobial Agents and Chemotherapy: 237(Abstract #731).
  6. Johnson, C.E.; et al.: Live Attenuated Varicella Vaccine in Healthy 12- to 24-Month-Old Children. Pediatrics. 81(4): 512-518, 1988.
  7. Gershon, A.A.; et al.: Immunization of Healthy Adults with Live Attenuated Varicella Vaccine. J Infect Dis. 158(1): 132-137, 1988.
  8. Gershon, A.A.; et al.: Live Attenuated Varicella Vaccine: Protection in Healthy Adults Compared with Leukemic Children. J Infect Dis. 161: 661-666, 1990.
  9. White, C.J.; et al.: Varicella Vaccine (VARIVAX) in Healthy Children and Adolescents: Results From Clinical Trials, 1987 to 1989. Pediatrics. 87(5): 604-610, 1991.
  10. Rynn L, Cragan J, Correa A. Update on Overall Prevalence of Major Birth Defects Atlanta, 1978-2005. CDC MMWR. 57(01): 1-5, January 11, 2008.
  11. American College of Obstetricians and Gynecologists Frequently Asked Questions: Miscarriage and Molar Pregnancy, 2011.
  12. Galea, S.; et al.: The Safety Profile of Varicella Vaccine: A 10-Year Review. J Infect Dis. 197(S2): 165-169, 2008.
  13. Hammerschlag, M.R.; et al.: Herpes Zoster in an Adult Recipient of Live Attenuated Varicella Vaccine. J Infect Dis. 160(3): 535-537, 1989.
  14. Guess, H.A.; et al.: Population-Based Studies of Varicella Complications. Pediatrics. 78(suppl): 723-727, 1986.
  15. Kuter, B.J.; et al.: Ten Year Follow-up of Healthy Children who Received One or Two Injections of Varicella Vaccine. Pediatr Infect Dis J. 23: 132-37, 2004.
  16. Kuter, B.J.; et al.: Oka/Merck Varicella Vaccine in Healthy Children: Final Report of a 2-Year Efficacy Study and 7-Year Follow-up Studies. Vaccine. 9: 643-647, 1991.
  17. Bernstein, H.H.; et al.: Clinical Survey of Natural Varicella Compared with Breakthrough Varicella After Immunization with Live Attenuated Oka/Merck Varicella Vaccine. Pediatrics. 92(6): 833-837, 1993.
  18. Wharton, M.: The Epidemiology of Varicella-zoster Virus Infections. Infect Dis Clin North Am. 10(3):571-581, 1996.
  19. White, C.J. et al.: Measles, Mumps, Rubella, and Varicella Combination Vaccine: Safety and Immunogenicity Alone and in Combination with Other Vaccines Given to Children. Clin Infect Dis. 24(5): 925-931, 1997.
  20. Reuman, P.D.; et al.: Safety and Immunogenicity of Concurrent Administration of Measles-Mumps-Rubella-Varicella Vaccine and PedvaxHIB® Vaccines in Healthy Children Twelve to Eighteen Months Old. Pediatr Infect Dis J. 16(7): 662-667, 1997.

VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Vaccine Sections

Vaccine Information by RSS

As the leading independent provider of trustworthy vaccine information, our database comes directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. VxLabels.com provides the full vaccine subset of the FDA's repository. Vaccine information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.