Clinical Immunotherapeutics

, Volume 4, Issue 5, pp 396–416

Oka/Merck Varicella Vaccine

A Review of its Immunogenicity and Protective Efficacy against Varicella

Authors

  • Caroline M. Perry
    • Adis International Limited
  • Harriet M. Bryson
    • Adis International Limited
Drug Evaluation

DOI: 10.1007/BF03259302

Cite this article as:
Perry, C.M. & Bryson, H.M. Clin Immunother (1995) 4: 396. doi:10.1007/BF03259302

Summary

Synopsis

Oka/Merck varicella vaccine is a live attenuated vaccine produced from the Oka strain of the herpesvirus varicella zoster virus (VZV). The Oka strain of VZV is recognised as having low virulence while eliciting humoral and cell-mediated responses to VZV. In numerous studies, Oka/Merck varicella vaccine achieved a seroconversion rate of >95% in healthy children and adolescents. In immunocompromised children with leukaemia in remission, seroconversion was achieved in 80% of vaccinees 12 months after vaccination. Cell-mediated immune responses generally closely paralleled humoral immune responses. The vaccine is also immunogenic in healthy adults.

In healthy children, a high level of protection was conferred by Oka/Merck varicella vaccine, and in the only double-blind placebo-controlled study conducted to date the vaccine was 98% effective in protecting healthy children against varicella during 2 varicella seasons. In children with leukaemia, Oka/Merck varicella vaccine was 80% effective in protecting against mild varicella and conferred 100% protection against moderate and severe varicella. In healthy adults, the rate of protection against varicella was reported to be approximately 50%. All observed cases of varicella in healthy and immunocompromised vaccinees were mild and there were no reports of any disease-related complications. Interestingly, in children and adolescents with leukaemia, the incidence of herpes zoster was lower in children who received Oka/Merck varicella vaccine than in similar children who had natural immunity.

Mild varicelliform rash (occasionally accompanied by fever) has been observed in healthy children, adolescents and adults who have received Oka/Merck varicella vaccine. Pain at the injection site was the adverse effect most frequently reported in one large study of the vaccine in healthy children. In children with leukaemia, vaccine-associated rash has been reported in up to 50% of vaccinees. When Oka/Merck varicella vaccine was administered to healthy children in combination with measles, mumps and rubella vaccine there was no increase in the incidence of skin rashes compared with that caused by measles, mumps and rubella vaccine in combination with placebo.

Thus, Oka/Merck varicella vaccine is a highly immunogenic vaccine that confers a high level of protection against typical varicella in healthy children and adolescents, and in children and adolescents with leukaemia. While results of further long term studies investigating the persistence of protective immunity against varicella are awaited with interest, available data indicate that Oka/Merck varicella vaccine is a major advance in the prevention of this common and highly infectious disease.

Immunogenicity

The immunogenicity of Oka/Merck varicella vaccine has been investigated in healthy children, adolescents and adults, and in children and adolescents with leukaemia. Six to 8 weeks after a single dose of Oka/Merck varicella vaccine [435 to 8700 plaque-forming units (pfu)] was administered to healthy children and adolescents, seroconversion rates of >95% were reported. Humoral and cell-mediated immunity to varicella has been shown to persist 20 years after 1 dose of 500 to 5000 pfu of Oka/Biken varicella vaccine (derived from the same ‘master seed’ as Oka/Merck varicella vaccine) administered to healthy children.

In immunocompromised children and adolescents with leukaemia, seroconversion rates of 72 and 100% were reported 18 months after one, or two to three, 1000 pfu doses of the vaccine, respectively. Thus, it appears that a second dose of the vaccine may be necessary for this patient group to achieve optimal seroconversion rates and cellular immune responses. In studies that monitored cellular immunity to varicella zoster virus (VZV), cell-mediated immune responses generally closely paralleled humoral immune responses.

A more vigorous antibody response occurs in healthy adolescents and adults after a second dose of Oka/Merck varicella vaccine. A recent study reported an increase in seroconversion rates from between 70 and 80% after 1 dose of the vaccine to 87 to 99% after a second dose given after 4 or 8 weeks. In healthy elderly individuals, Oka/Merck varicella vaccine elicited a persistent booster cell-mediated immune response.

Protective Efficacy

The protective efficacy of Oka/Merck varicella vaccine has been determined by comparing the varicella attack rate in vaccine recipients after exposure to VZV-infected individuals (usually in the household setting) with that in unvaccinated susceptible individuals. A single dose of Oka/Merck varicella vaccine administered to healthy children and adolescents was highly protective against clinical varicella. A high-dose formulation of Oka/Merck varicella vaccine (8700 pfu) was 98% effective in protecting children against varicella during 2 varicella seasons in a double-blind placebo-controlled trial.

Oka/Merck varicella vaccine is also effective in protecting children with leukaemia in remission, a patient group that is at increased risk of developing severe varicella. One study reported that one to three 1000 pfu doses of Oka/Merck varicella vaccine were 100% effective in preventing moderate and severe varicella and 80% effective in protecting against mild varicella. In a large study that compared the incidence of herpes zoster in vaccinated children with leukaemia in remission with that in similar children who had previously had natural varicella, there was a higher incidence of herpes zoster in children with natural immunity. In adults, protection against varicella was conferred in 45 to 51% of vaccinees. Following vaccination of healthy children, adolescents and adults, as well as children and adolescents with leukaemia, cases of varicella were characteristically mild and there were no reports of any disease-related complications.

The economic implications of a universal varicella vaccination campaign in the US have been determined in several studies. Although varicella vaccination has been shown not to be cost effective from a healthcare payer’s perspective, studies which took a societal perspective demonstrated that a vaccination policy was highly cost effective, saving the US an estimated US$400 million per year.

Tolerability

Oka/Merck varicella vaccine is well tolerated by healthy children, adolescents and adults, with pain at the site of injection being reported as the most common adverse effect. Mild varicelliform rash (occasionally accompanied by fever) occurs in 5 to 10% of healthy individuals in all age groups. In children with leukaemia, rashes have been reported in up to 50% of vaccinees. These rashes tend to be more severe than in healthy individuals and may require treatment with an antiviral agent. The incidence of vaccine-associated rash in children with leukaemia is significantly increased by steroid administration within 3 weeks of vaccination and may be increased in individuals who receive antineoplastic drug treatment after vaccination.

Severe rash was not reported after simultaneous administration of Oka/Merck varicella vaccine with the trivalent measles, mumps and rubella vaccine. There were no significant differences in the incidences of skin rash and fever between recipients of measles, mumps and rubella vaccine with placebo and recipients of measles, mumps and rubella vaccine with Oka/Merck varicella vaccine.

Dosage and Administration

Oka/Merck varicella vaccine contains a minimum of 1350 pfu/0.5ml. The recommended dose for healthy infants and children aged between 1 and 12 years is 0.5ml, which should be administered subcutaneously. The vaccine should preferably be administered to infants aged 12 to 18 months at the same time as the measles, mumps and rubella vaccine. Healthy adolescents aged ≥13 years and adults should receive a second dose of Oka/Merck varicella vaccine 4 to 8 weeks after the first dose. Children and adolescents with acute lymphoblastic leukaemia in remission may receive Oka/Merck varicella vaccine under an investigational protocol only. As Oka/Merck varicella vaccine contains trace quantities of neomycin, it should not be administered to individuals with a history of anaphylactic reaction to neomycin.

Copyright information

© Adis International Limited 1995