Live varicella vaccine in healthy individuals.

Eight hundred healthy seronegative children and 32 adults were vaccinated with the Oka-strain live attenuated varicella vaccine (Varilrix), manufactured by Smith Kline-RIT, Belgium. The vaccine was safe (no side effects) in healthy individuals, highly immunogenic (dose-dependent induction of humoral antibodies and specific cell-mediated immune response), and highly protective against clinical varicella. The simultaneous administration of a measles-mumps-rubella vaccine together with the varicella vaccine is possible, although combination in the same syringe was less effective than simultaneous administration in different arms. Various observations suggest that the risk of contracting zoster in adulthood may well be reduced for varicella vaccinees. Based on our results, it is recommended that seronegative hospital staff be vaccinated. Furthermore, if the varicella vaccine should prove to be cost effective, large-scale immunization of healthy children may be indicated.

Delayed hypersensitivity skin test to detect susceptibility to varicella and zoster.

A crude varicella skin-test antigen corresponding to an inactivated partly-purified high-titre varicella Oka-strain vaccine was prepared at Smith Kline-RIT. It was used for a delayed hypersensitivity skin test in 60 healthy adults for determination of their immune status. The findings were analysed according to the presence or absence of humoral antibodies to varicella-zoster virus (VZV), and of a specific cell-mediated immune (CMI) response as measured by the VZV-specific lymphocyte transformation test. The immune status to varicella could be determined in all subjects provided that the amount of antigenic material in the skin-test antigen was sufficiently high. The 2 tests for the CMI response, the delayed hypersensitivity skin test and the lymphocyte transformation test, gave concordant results in both seropositive and seronegative individuals. The inactivated skin-test antigen cannot replace vaccination with the live varicella vaccine since it is unable to induce seroconversion in seronegatives or an antibody booster response in seropositives. Furthermore, seropositive and seronegative subjects showing a negative response to the varicella-zoster-specific lymphocyte transformation test remained negative 2 weeks after the injection of the skin-test antigen.

Restoration of varicella-zoster virus cell-mediated immune response after varicella booster vaccination.

In older age groups, an increasing proportion of healthy adults with a positive varicella history have lost their capacity for a cell-mediated immune (CMI) response to varicella-zoster virus (VZV) antigen despite the presence of virus-specific humoral antibodies. While it remains a matter of speculation whether this decline is connected with a predisposition to herpes zoster, it is known that a second zoster attack is rare in immunocompetent individuals. In order to determine whether the VZV-specific CMI response can be restored through varicella vaccination, the immune status of a group with naturally occurring herpes zoster was compared with that of a group of vaccinated subjects. Twenty zoster patients were tested for VZV antibody and VZV-specific CMI within the first 4 days of the disease. Antibodies were present in normal or moderately high titres (mean: 2,900). Lymphocyte reactivity to VZV antigen was negative or weakly positive in 17 of the 20 patients. After 6 weeks, antibody titres rose significantly (mean: 36,000) and the lymphocyte response was highly positive in 11, weakly positive in 6, and remained negative in 3 patients. Thirty-three healthy adults ranging in age from 55-65 years with a negative VZV-specific CMI, but positive VZV antibodies (mean: 190), were immunized with the Oka-strain varicella vaccine (Varilrix). After 6 weeks, the mean antibody titre had only increased slightly (mean: 400). However, a positive VZV-specific CMI response occurred in 28 out of 33 subjects, while 5 remained negative. Therefore, conversion from a negative to a positive CMI response can be achieved by varicella vaccination of seropositive subjects. This raises the question whether booster vaccination of CMI-negative subjects could prevent zoster.

OKA-SK-RIT Varicella vaccine for "primary" and for booster vaccinations.

In seronegative children--healthy and immunocompromised--and in seronegative adults, we have limited but very promising results--no side reactions and good antibody-conversions with clinical protection. Because--in spite of positive humoral antibodies--10 to 20% of people over the age of 50 have a negative cell-mediated immune response against VZ and are therefore presumed Zoster patients, VZ-booster vaccinations were done in this age group. A significant increase in humoral antibodies can be induced at least in half of these elderly. In 23 elderly with a negative specific cell-mediated immunity against VZ, a booster vaccination induced a strong positive cell-mediated immune response in 9 and no response in 5.