GSK
Infanrix hexa Synflorix Havrix Varilrix
Protection Against Varicella in Healthy Children: A Double-Blind Placebo-Controlled Vaccine Trial

Protection Against Varicella in Healthy Children: A Double-Blind Placebo-Controlled Vaccine Trial

Article For Year 2 Vaccination 5 min read
Tagged Article Varicella Year 2 Vaccination
V
Authored by GSK Vaxipedia
Varilrix
In this article

Introduction

Varicella, commonly known as chickenpox, is a highly contagious infection caused by the varicella-zoster virus (VZV). It is characterized by a distinctive vesicular rash that progresses into pruritic, fluid-filled lesions which eventually crust over. The rash typically begins on the chest, back, or face and subsequently spreads to the entire body.

Although often self-limiting, varicella can lead to serious complications such as pneumonia, secondary bacterial infections, and, in severe cases, mortality. The World Health Organization (WHO) reports a substantial global burden of varicella, with millions of severe complications and thousands of deaths occurring each year. Since the introduction of the live attenuated varicella vaccine in the 1970s, widespread immunization programs have led to a marked decline in varicella incidence across many countries.1,2

The WHO recommends incorporating varicella vaccines into universal immunization programs and maintaining coverage levels above 80%.3 In the United States, licensed vaccines include the single-antigen varicella vaccine and the combined measles, mumps, rubella, and varicella (MMRV) vaccine, approved for use in children aged 1-12 years. Administration of two doses provides approximately 90% protection against varicella.4

Immunization Schedule (IAP 2022)

Primary Immunization

According to the Indian Academy of Pediatrics, the first dose is recommended at 15 months, followed by a second dose administered preferably 3-6 months later to prevent breakthrough varicella and immunization failure.

Catch-up Vaccination

  • <13 years: Two doses administered 3 months apart
  • ≥13 years: Two doses administered 4-8 weeks apart

Post-exposure Vaccination

  • Should be given within 3-5 days of exposure.5

Live-Attenuated Varicella Vaccine: Proven Safety, Strong Immunity, Effective Protection6

Study design and population

This multicenter, double-blind, placebo-controlled trial enrolled 5997 healthy children aged 1-12 years who were seronegative for VZV. Participants were randomized to receive either a single dose of live attenuated varicella vaccine (n = 2995) or placebo (n = 2996) and were followed for the occurrence of laboratory-confirmed varicella infection.

Clinical Outcomes

Vaccine Efficacy

Endpoint

Vaccine (n=2995)

Placebo (n=2996)

Protective Efficacy (%) (95% CI)

Laboratory-confirmed varicella

6

46

87.1 (69.7–94.5)

Children 1–4 years

2

11

80.2 (10.7–95.6)

Children 5–8 years

3

25

88.6 (62.2–96.6)

Children 9–12 years

1

10

90.2 (23.4–98.7)

Breakthrough varicella

5

46

89.2 (72.9–95.7)

Children 1–4 years

1

11

90.1 (23.3–98.7)

Children 5–8 years

3

25

88.6 (62.2–96.6)

Children 9–12 years

1

10

90.2 (23.4–98.7)

A total of 52 laboratory-confirmed cases were reported, including 6 in the vaccine group and 46 in the placebo group, with 51 cases occurring after day 42. The overall vaccine efficacy was 87.1% (95% CI: 69.7–94.5) and 89.2% (95% CI: 72.9–95.7) against breakthrough varicella. Age-stratified analysis demonstrated consistently high efficacy across all groups: 80.2% (1–4 years), 88.6% (5–8 years), and 90.2% (9–12 years).6

Immunogenicity

  • Post-vaccination, seropositivity increased significantly to 99.4% in the vaccine group compared to 72.0% in the placebo group.
  • The vaccine induced a strong immune response, with a seroconversion rate of 97.1% and significantly higher antibody titers (GMT: 46.5 vs. 8.4; p < 0.001).
  • Among susceptible children, seroconversion reached 98.0%, while a ≥4-fold rise in antibody levels was observed in 96.8% of the non-susceptible population.
  • An antibody titer of 1:8 was identified as a potential correlate of protection against Varicella, highlighting the vaccine’s ability to generate robust and protective immune responses.

Safety

  • The live attenuated varicella vaccine demonstrated a favorable safety profile. A total of 490 solicited adverse reactions were reported in the vaccine group compared to 519 in the placebo group.
  • Grade 3 adverse events within 14 days after vaccination were rare, occurring in 0.1% of vaccine recipients and 0.2% of placebo recipients.
  • The most common local reactions included redness, pain, and erythema, while systemic reactions primarily included fever, cough, and diarrhea.
  • Serious adverse events were comparable between groups (0.8% vs. 0.7%), with only one case considered possibly vaccine-related, which fully resolved.
  • No significant differences were observed between groups in terms of local or systemic reactions.

Conclusion

The live attenuated varicella vaccine demonstrates high efficacy, strong immunogenicity, and an excellent safety profile in healthy children. It significantly reduces the incidence of Varicella, with protective efficacy exceeding 85% and consistent effectiveness across all pediatric age groups. The vaccine induces robust immune responses, characterized by high seroconversion rates and sustained antibody levels, ensuring reliable protection. Although antibody levels and occasional breakthrough cases may occur, the overall disease burden is substantially reduced. These findings support the widespread use of varicella vaccination as an effective strategy for preventing infection, minimizing complications, and controlling outbreaks in pediatric populations.

References

  1. Bolormaa E, Lee YH, Choe YJ, Choe SA. Varicella Vaccine Effectiveness and Duration of Protection: A Systematic Review and Meta-Analysis. J Korean Med Sci. 2025;40(44):e286. Published 2025 Nov 17. doi:10.3346/jkms.2025.40.e286.
  2. Centers for Disease Control and Prevention. Clinical features of chickenpox (varicella). Updated June 5, 2024. Accessed March 31, 2026.
  3. Wutzler P, Bonanni P, Burgess M, Gershon A, Sáfadi MA, Casabona G. Varicella vaccination - the global experience. Expert Rev Vaccines. 2017;16(8):833-843. doi:10.1080/14760584.2017.1343669
  4. Centers for Disease Control and Prevention. Varicella vaccine recommendations. Updated July 15, 2024. Accessed March 31, 2026.
  5. Varicella. India Academy of Pediatrics. 2022. Accessed April 2, 2026. https://iapindia.org/pdf/Ch-050-stg-varicella.pdf
  6. Hao B, Chen Z, Zeng G, et al. Efficacy, safety and immunogenicity of live attenuated varicella vaccine in healthy children in China: double-blind, randomized, placebo-controlled clinical trial. Clin Microbiol Infect. 2019;25(8):1026-1031. doi:10.1016/j.cmi.2018.12.033.

Disclaimer

For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information. Please report adverse events with any GSK product to the company at india.pharmacovigilance@gsk.com 2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).

For Healthcare Professionals Only

Key Safety Information

Contraindications:

Hypersensitivity to any active substance or excipient or neomycin. or varicella vaccine. Primary or acquired immunodeficiency who have total lymphocyte count <1200 per mm3 or other evidence of lack of cellular immune competence or subjects receiving immunosuppressive therapy (including high dose corticosteroids).

Pregnancy:

Avoid pregnancy for 1 month following vaccination.

Special warnings and precautions:

Postpone administration in acute febrile illness. Syncope (fainting) can occur following, or even before any vaccination, with adolescents, as a psychogenic reaction to injection. Avoid all contact with pregnant women susceptible to varicella (especially during first trimester pregnancy) and with high risk for developing severe varicella, especially when person vaccinated develops skin eruption within 2 to 3 weeks of immunization. To reduce infection risk of high-risk subjects, non-immune persons living in close contact with varicella patients or high-risk patients should be vaccinated. A decision should be made either to discontinue breastfeeding or to abstain from vaccination with VARILRIX, taking into account the benefit of breastfeeding for the child with regard to the benefit of prophylaxis against Varicella for the woman.

Undesirable effects: Very common- redness, pain at the injection site.

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

Abbreviated Prescribing information of VARILRIX (Varicella Vaccine, Live IP)

ACTIVE INGREDIENT: Each 0.5 ml of the reconstituted vaccine contains: Live attenuated varicella virus (OKA strain, propagated in MRC5 human diploid cells) not less than 103.3 plaque-forming units (PFU).

INDICATION: VARILRIX is indicated for active immunisation against varicella of healthy subjects and susceptible healthy close contacts from the age of 12 months onwards. Susceptible healthy close contacts should be immunised in order to reduce the risk of transmission of virus to high-risk patients. These include parents and siblings of high-risk patients, and medical, paramedical personnel and other people who are in close contact with varicella patients or high-risk patients.

POSOLOGY AND ADMINISTRATION: Posology: The immunisation schedules for VARILRIX should be based on official recommendations. Healthy individuals: Children from 12 months of age, adolescents and adults: Children from the age of 12 months as well as adolescents and adults receive two doses of VARILRIX to ensure optimal protection against varicella. The second dose should generally be given at least 6 weeks after the first dose. Under no circumstances should the interval between the doses be less than 4 weeks. Individuals at high risk of severe varicella: Individuals at high risk of severe varicella may benefit from re-vaccination following the 2-dose schedule. Periodic measurement of varicella antibodies after immunisation may be indicated in order to identify those who may benefit from re-immunisation. Under no circumstances should the interval between the doses be less than 4 weeks. Interchangeability: A single dose of VARILRIX may be administered to subjects who have already received a single dose of another varicella-containing vaccine. A single dose of VARILRIX may be administered followed by a single dose of another varicella-containing vaccine. Method of administration: VARILRIX is to be injected subcutaneously (SC) in the deltoid region or in the anterolateral area of the thigh.

CONTRA-INDICATIONS: VARILRIX is contraindicated in individuals with severe humoral or cellular (primary or acquired) immunodeficiency such as: subjects with immunodeficiency states with a total lymphocyte count less than 1,200 per mm3; subjects presenting other evidence of lack of cellular immune competence (e.g. patients with leukaemias, lymphomas, blood dyscrasias, clinically manifest HIV infection); subjects receiving immunosuppressive therapy including high dose of corticosteroids; severe combined immunodeficiency; agammaglobulinemia; AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15%. Hypersensitivity to the active substance or to any of the excipients or to neomycin. However, a history of contact dermatitis to neomycin is not a contraindication. VARILRIX is contraindicated in subjects having shown signs of hypersensitivity after previous administration of varicella vaccine. Pregnancy- Furthermore, pregnancy should be avoided for 1 month following vaccination.

SPECIAL WARNINGS and SPECIAL PRECAUTIONS: As with other vaccines, the administration of VARILRIX should be postponed in subjects suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

Syncope (fainting) can occur following, or even before any vaccination especially in adolescents as a psychogenic response to the needle injection. This can be accompanied by several neurological signs such as transient visual disturbances, paraesthesia and tonic-clonic movements during recovery. It is important that procedures are in place to avoid injury from faints. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic reaction following the administration of the vaccine. Alcohol and other disinfecting agents must be allowed to evaporate from the skin before injection of the vaccine since they can inactivate the attenuated viruses in the vaccine. Limited protection against varicella may be obtained by vaccination up to 72 hours after exposure to natural disease. As with any vaccine, a protective immune response may not be elicited in all vaccinees. As for other varicella vaccines, cases of varicella disease have been shown to occur in persons who have previously received VARILRIX. These breakthrough cases are usually mild, with a fewer number of lesions and less fever as compared to cases in unvaccinated individuals. Transmission: Transmission of the Oka varicella vaccine virus has been shown to occur at a very low rate in seronegative contacts of vaccinees with rash. Transmission of the Oka varicella vaccine virus from a vaccinee who does not develop a rash to seronegative contacts cannot be excluded.

Compared to healthy vaccinees, leukaemia patients are more likely to develop a papulovesicular rash. In these cases too, the course of the disease in the contacts was mild. Vaccine recipients, even those who do not develop a varicella-like rash, should attempt to avoid contact, whenever possible, with high-risk individuals susceptible to varicella for up to 6 weeks following vaccination. In circumstances where contact with high-risk individuals susceptible to varicella is unavoidable, the potential risk of transmission of the varicella vaccine virus should be weighed against the risk of acquiring and transmitting wild-type varicella virus. High-risk individuals susceptible to varicella include: Immunocompromised individuals; Pregnant women without documented positive history of varicella (chickenpox) or laboratory evidence of prior infection; Newborns of mothers without documented positive history of chickenpox or laboratory evidence of prior infection. The mild nature of the rash in the healthy contacts indicates that the virus remains attenuated after passage through human hosts. Individuals at high risk of severe varicella: There is only limited data from clinical trials available for VARILRIX (+4°C formulation) in individuals at high risk of severe varicella.

Vaccination may be considered in patients with selected immune deficiencies where the benefits outweigh the risks (e.g. asymptomatic HIV subjects, IgG subclass deficiencies, congenital neutropenia, chronic granulomatous disease, and complement deficiency diseases). Immunocompromised patients who have no contraindication for this vaccination may not respond as well as immunocompetent subjects, therefore some of these patients may acquire varicella in case of contact, despite appropriate vaccine administration. These patients should be monitored carefully for signs of varicella. Should vaccination be considered in individuals at high risk of severe varicella, it is advised that: maintenance chemotherapy should be withheld one week before and one week after immunisation of patients in the acute phase of leukaemia. Patients under radiotherapy should normally not be vaccinated during the treatment phase. Generally, patients are immunised when they are in complete haematological remission from their disease. The total lymphocyte count should be at least 1,200 per mm3 or no other evidence of lack of cellular immune competence exists. Vaccination should be carried out a few weeks before the administration of the immunosuppressive treatment for patients undergoing organ transplantation (e.g. kidney transplant). Very few reports exist on disseminated varicella with internal organ involvement following vaccination with Oka varicella vaccine strain mainly in immunocompromised subjects. VARILRIX must not be administered intravascularly or intradermally. Phenylalanine content: The vaccine contains 331 micrograms of phenylalanine per dose. Phenylalanine may be harmful for individuals with phenylketonuria (PKU).

ADVERSE EFFECTS: Very common (≥1/10): pain, erythema. Common (≥1/100 to <1/10): Rash, Pyrexia (oral / axillary temperature ≥ 37.5 °C or rectal temperature ≥ 38.0 °C)†, injection site swelling† Uncommon (≥1/1,000 to <1/100): upper respiratory tract infection, pharyngitis, lymphadenopathy, irritability, headaches, somnolence, cough, rhinitis, nausea, vomiting, viral rash, pruritus, myalgia, arthralgia, Pyrexia (oral / axillary temperature> 39.0°C or rectal temperature> 39.5°C), fatigue, malaise. Rare (≥1/10,000 to < 1/1,000): conjunctivitis, abdominal pain, diarrhea, urticaria.

According to MedDRA (Medical Dictionary for Regulatory Activities) terminology. Injection site swelling and pyrexia were reported very commonly in studies conducted in adolescents and adults. Injection site swelling was also reported very commonly after the second dose in children under 13 years of age.

Version: VRX/API/IN/2025/02 v02 dated 16-Oct-2025

Refer to full prescribing information before prescribing.

Registered medical practitioners can refer company website http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information.

Please report adverse events with any GSK product to the company at india.pharmacovigilance@gsk.com

For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website: india-pharma.gsk.com/en-in/products/prescribing-information/ for Full Product Information. Please report adverse events with any GSK product to the company at india.pharmacovigilance@gsk.com. ©2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).