Varicella-zoster virus (VZV) vaccines induce immunity against childhood chickenpox and against shingles in older adults. The safety, efficacy, and widespread use of VZV vaccines suggest that they may also be effective as recombinant vaccines against other infectious diseases that affect the young and the elderly. The generation of recombinant VZV vaccines and their evaluation in animal models are reviewed. The potential advantages and limitations of recombinant VZV vaccines are addressed. 1. Introduction Varicella-zoster virus (VZV) vaccines provide immune protection against diseases that affect both the young and the elderly. The live, attenuated varicella vaccine (VARIVAX) immunizes children against chickenpox, a childhood disease characterized by fever and vesicular skin rash. The VZV Zostavax vaccine protects older adults against herpes zoster (shingles), a vesicular skin disease caused by VZV reactivation from latently infected neural ganglia. The proven safety and effectiveness of the varicella and shingles vaccines provide support for recombinant VZV (rVZV) vaccines to induce immunity against not only VZV but also against other pathogens. The ability of VZV vaccines to safely induce long-lasting humoral and cellular immune responses provides advantages over other live, attenuated vaccine vectors and over killed and subunit vaccines. This review summarizes research to develop and evaluate VZV vectors as recombinant vaccines against other diseases. 1.1. Varicella and Herpes Zoster Varicella is a highly contagious disease of children and adolescents [1]. The infectious agent is transmitted through aerosols by coughs and sneezes or by direct contact with rash secretions. Following a 10–14 day incubation period, fever and malaise arise along with the characteristic vesicular skin rash, which occurs on the face, torso, and extremities. Chickenpox is generally a benign disease in otherwise healthy children with symptoms usually completely resolved within two weeks of disease onset and with subsequent life-long immunity against varicella. However, complications may include varicella pneumonia, hepatitis, encephalitis, and secondary bacterial infections. Immunocompromised children, including cancer and AIDS patients, are particularly susceptible to severe, sometimes life-threatening varicella [2, 3]. Adults who escape VZV exposure during childhood have more severe varicella symptoms and complications. VZV infection in pregnant women during the first 28 weeks of gestation may lead to fetal infection and congenital malformations [4]. Later maternal
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