Reactogenicity and immunogenicity of a live attenuated tetravalent measles–mumps–rubella–varicella (MMRV) vaccine
Introduction
Chickenpox, or primary infection with the varicella-zoster virus (VZV), is a highly contagious disease characterised by fever, malaise, and a generalised vesicular rash. The disease is usually self-limiting, but infants, adolescents, adults, and immunocompromised persons are at higher risk of complications if infected.
Live, attenuated varicella vaccines (derived from the Oka strain) are registered in many countries worldwide, although their routine use is only recommended in some countries, including the United States. Varicella vaccines are usually indicated from the age of 12 months, which is also the age indication for the first dose of combined measles–mumps–rubella (MMR) vaccine [1], [2]. Availability of a combined measles–mumps–rubella–varicella (MMRV) vaccine would facilitate the introduction of varicella vaccine into national childhood immunisation schedules without an increase in the required number of injections or visits to the health care provider.
The Scientific Advisory Group of Experts (SAGE) of the World Health Organisation’s Global Program on Vaccination states that ‘new vaccines should be introduced into national programs in a manner which does not jeopardise current immunisation priorities’ [3]. Childhood combination vaccines, with minimal local and systemic adverse reactions, are more likely to be acceptable to both parents and vaccine providers [4], and may therefore increase compliance with crowded immunisation schedules [5].
Measles–mumps–rubella–varicella combinations have been investigated previously [6], [7], [8], [9], [10]. However, an acceptable tetravalent vaccine formulation, in terms of reactogenicity and immunogenicity, is yet to be identified. In this study, we evaluated the safety and immunogenicity of a live attenuated tetravalent MMRV vaccine and an extemporaneous mix of MMR vaccine and varicella vaccine (MMR/V) compared with trivalent MMR vaccine alone.
Section snippets
Trial design and subjects
This was a single-blind randomised multicentre study with three groups of 80 children enrolled through three Australian tertiary paediatric centres, the Royal Children’s Hospital in Melbourne, the Royal Alexandra Hospital for Children in Sydney, and the Women’s and Children’s Hospital in Adelaide. The study was approved by the respective ethics review committee for each trial centre. Healthy male and female children aged 12 months were enrolled according to a blocked randomisation, six subjects
Enrolment and attrition
The study was conducted between October 1997 and May 1998. A total of 240 children were enrolled and were randomised for vaccination—80 into each of the three study groups. There were no important differences in baseline demographic characteristics between study group subjects. The mean age of all participants was 12.1 months and 57.9% of children were female. Two participants were lost to follow-up at the final study visit, three subjects received a non-study vaccine during the follow-up
Discussion
With the widespread availability of monovalent varicella vaccines, the possibility exists for greatly enhanced control of chickenpox, and perhaps prevention of herpes zoster (shingles) in later life. However, widespread use of varicella vaccine will substantially depend on its inclusion on national childhood immunisation schedules. Although live, attenuated varicella vaccines (derived from the Oka strain) are available in many countries, universal recommendation of their routine use is not
Acknowledgements
The following are gratefully acknowledged for contributing in many ways to this study: Jacqueline Aldis, Dr. Christina Boros, Leonie Dinan, Dr. Raewyn Garin, Dr. Michael Gold, Lindy Harkness, Dr. Helen Marshall, Anna Pisaniello, Dr. Michelle Tilley (Women’s and Children’s Hospital, Adelaide); the many Melbourne Maternal and Child Health Nurses who assisted in subject recruitment, Dr. Anne Altmann, Jennifer Foord, Rosie Gehrig-Mills, Debbie Gerkovich, Dr. Len Hartman, Associate Prof. Geoff Hogg,
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